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d-Amino acids, rare enantiomers of amino acids, have been identified as biomarkers and therapeutic options for COVID-19. Methods for monitoring recovery are necessary for managing COVID-19. On the other hand, the presence of SARS-CoV2 virus in the blood is associated with worse outcomes. We investigated the potential of d-amino acids for assessing recovery from severe COVID-19. In patients with severe COVID-19 requiring artificial ventilation, the blood levels of d-amino acids, including d-alanine, d-proline, d-serine, and d-asparagine, which were lower than the normal range before treatment, quickly and transiently increased and surpassed the upper limit of the normal range. This increase preceded the recovery of respiratory function, as indicated by ventilation weaning. The increase in blood d-amino acid levels was associated with the disappearance of the virus in the blood, but not with inflammatory manifestations or blood cytokine levels. d-Amino acids are sensitive biomarkers that reflect the recovery of the clinical course and blood viral load. Dynamic changes in blood d-amino acid levels are key indicators of clinical course., Competing Interests: TK, YI, SKO are preparing for the patent application, which is related with this work. TK has an equity in KAGAMI Inc. The authors declare no other competing interests.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomonori Kimura reports a relationship with KAGAMI Inc that includes: equity or stocks. Tomonori Kimura and Shihoko Kimura-Ohba have patent pending to NIBIOHN. Yoshitaka Isaka has a patent pending to Osaka University., (© 2023 The Authors.)

COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 Elsevier B.V. All rights reserved.)

Introduction: As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread around the world, patient care was shifted to outpatient care and home monitoring. This paper describes the characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) treated at home during the second and third waves in Saudi Arabia., Materials and Methods: Descriptive evaluation of the characteristics and outcome of COVID-19-positive cases enrolled in the home monitoring programme., Results: This study included 14,970 SARS-CoV-2-positive patients (52.6% male). The mean age was 30.8 [standard deviation (SD) 19.9] years. Among the confirmed cases, 14,234 had documented vaccination status; of these, 3943 (27.7%) had not received any doses of COVID-19 vaccine, 1452 (10.2%) had received one dose, 4882 (34.3%) had received two doses, and 3957 (27.8%) had received three doses. The mean number of days in the home monitoring programme was 8.3 (SD 3.5) days. The mean interval from the last vaccine dose until SARS-CoV-2 infection was 116.6 (SD 75.5) days in 7975 patients. The presence of comorbidities was as follows: chronic kidney disease, 340 (2.3%); hypertension, 2569 (17.2%); chronic pulmonary disease, 2539 (17%); smoking, 1711 (11.4%) of 9269 with documented smoking histroy; coronary artery disease, 854 (5.7%); and diabetes mellitus, 1531 (10.3%). The hospitalization rate was 1.8%, and the case fatality rate was 5% of admitted patients, accounting for 0.11% of all cases. The mean age of patients who died was 76.6 (SD 17.7) years, which was higher compared with the mean age of those who survived [30.8 (SD 19.9) years] ( P <0.001)., Conclusion: Utilization of a home monitoring programme was effective and safe for patients with COVID-19 who were either asymptomatic or had mild symptoms., (© 2023 The Author(s).)

Previous data have suggested an antiviral effect of teriflunomide, including against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the agent underlying the ongoing COVID-19 pandemic. We undertook an in vitro investigation to evaluate the inhibitory activity of teriflunomide against SARS-CoV-2 in a cell-based assay. Teriflunomide was added to Vero (kidney epithelial) cells that had been infected with SARS-CoV-2. A nucleocapsid immunofluorescence assay was performed to examine viral inhibition with teriflunomide and any potential cytotoxic effect. The 50% effective concentration (EC 50 ) for teriflunomide against SARS-CoV-2 was 15.22 μM. No cytotoxicity was evident for teriflunomide in the Vero cells (i.e., the 50% cytotoxic concentration [CC 50 ] was greater than the highest test concentration of 100 μM). The data were supported by additional experiments using other coronaviruses and human cell lines. In the SARS-CoV-2-infected Vero cells, the prodrug leflunomide had an EC 50 of 16.49 μM and a CC 50 of 54.80 μM. Our finding of teriflunomide-mediated inhibition of SARS-CoV-2 infection at double-digit micromolar potency adds to a growing body of evidence for a broad-ranging antiviral effect of teriflunomide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul Lang, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Paul Lang, PhD reports a relationship with Sanofi that includes: employment. Svend S. Geertsen, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Svend S. Geertsen, PhD reports a relationship with Sanofi that includes: employment. Alex L. Lublin, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Alex L. Lublin, PhD reports a relationship with Sanofi that includes: employment. Michelle C. Potter, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Michelle C. Potter, PhD reports a relationship with Sanofi that includes: employment. Tatiana Gladysheva reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Tatiana Gladysheva reports a relationship with Sanofi that includes: employment. Jill S. Gregory reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Jill S. Gregory reports a relationship with Sanofi that includes: employment. Pascal Rufi, MD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Pascal Rufi, MD reports a relationship with Sanofi that includes: employment., (© 2022 Published by Elsevier B.V.)

Besides its use against HIV infection the marketed anti-retroviral drug dolutegravir attracted attention as a potential agent against COVID-19 in multiple AI (artificial intelligence) based studies. Due to our interest in accessing the impurities of this drug we report the synthesis and characterization of three impurities of dolutegravir one of which is new. The synthesis of O-methyl ent-dolutegravir was accomplished in three-steps the first one involved the construction of fused 1,3-oxazinane ring. The cleavage of -OEt ether moiety followed by methylation afforded the target compound. The second impurity i.e. N -(2,4-difluorobenzyl)-4-methoxy-3-oxobutanamide was synthesized via a multi-step method involving sequentially the keto group protection, ester hydrolysis, acid chloride formation followed by the reaction with amine and finally keto group deprotection. The synthesis of new or dimer impurity was carried out via another multi-step method similar to the previous one starting from ethyl 4-chloro acetoacetate. The methodology involved preparation of ether derivative, keto group protection, ester hydrolysis, preparation of amide derivative via acid chloride formation in situ and then keto group deprotection for a longer duration. The last step afforded the target compound for which a plausible reaction mechanism has been proposed. All three impurities were prepared in gram scale (minimum 2 g and maximum 8 g). The in silico evaluation of three selected synthesized intermediates e.g. 7, 8 and 9 (structurally similar to dolutegravir) against SARS CoV-2 O-ribose methyltransferase (OMTase) (PDB: 3R24) indicated that compound 7 could be of interest as a possible inhibitor of this protein., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Fructose-rich beverages and foods consumption correlates with the epidemic rise in cardiovascular disease, diabetes and obesity. Severity of COVID-19 has been related to these metabolic diseases. Fructose-rich foods could place people at an increased risk for severe COVID-19. We investigated whether maternal fructose intake in offspring affects hepatic and ileal gene expression of proteins that permit SARS-CoV2 entry to the cell. Carbohydrates were supplied to pregnant rats in drinking water. Adult and young male descendants subjected to water, liquid fructose alone or as a part of a Western diet, were studied. Maternal fructose reduced hepatic SARS-CoV2 entry factors expression in older offspring. On the contrary, maternal fructose boosted the Western diet-induced increase in viral entry factors expression in ileum of young descendants. Maternal fructose intake produced a fetal programming that increases hepatic viral protection and, in contrast, exacerbates fructose plus cholesterol-induced diminution in SARS-CoV2 protection in small intestine of progeny., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objectives: We performed a virtual screening of olive secoiridoids of the OliveNet TM library to predict SARS-CoV-2 PLpro inhibition. Benchmarked molecular docking protocol that evaluated the performance of two docking programs was applied to execute virtual screening. Molecular dynamics stability analysis of the top-ranked olive secoiridoid docked to PLpro was also carried out., Methods: Benchmarking virtual screening used two freely available docking programs, AutoDock Vina 1.1.2. and AutoDock 4.2.1. for molecular docking of olive secoiridoids to a single PLpro structure. Screening also included benchmark structures of known active and decoy molecules from the DEKOIS 2.0 library. Based on the predicted binding energies, the docking programs ranked the screened molecules. We applied the usual performance evaluation metrices to evaluate the docking programs using the predicted ranks. Molecular dynamics of the top-ranked olive secoiridoid bound to PLpro and computation of MM-GBSA energy using three iterations during the last 50 ps of the analysis of the dynamics in Desmond supported the stability prediction., Results and Discussions: Predictiveness curves suggested that AutoDock Vina has a better predictive ability than AutoDock, although there was a moderate correlation between the active molecules rankings (Kendall's correlation of rank (τ) = 0.581). Interestingly, two same molecules, Demethyloleuropein aglycone, and Oleuroside enriched the top 1 % ranked olive secoiridoids predicted by both programs. Demethyloleuropein aglycone bound to PLpro obtained by docking in AutoDock Vina when analyzed for stability by molecular dynamics simulation for 50 ns displayed an RMSD, RMSF<2 Å, and MM-GBSA energy of -94.54 ± 6.05 kcal/mol indicating good stability. Molecular dynamics also revealed the interactions of Demethyloleuropein aglycone with binding sites 2 and 3 of PLpro, suggesting a potent inhibition. In addition, for 98 % of the simulation time, two phenolic hydroxy groups of Demethyloleuropein aglycone maintained two hydrogen bonds with Asp302 of PLpro, specifying the significance of the groups in receptor binding., Conclusion: AutoDock Vina retrieved the active molecules accurately and predicted Demethyloleuropein aglycone as the best inhibitor of PLpro. The Arabian diet consisting of olive products rich in secoiridoids benefits from the PLpro inhibition property and reduces the risk of viral infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The COVID-19 pandemic highlighted public awareness of airborne disease transmission in indoor settings and emphasized the need for reliable air disinfection technologies. This increased awareness will carry in the post-pandemic era along with the ever-emerging SARS-CoV variants, necessitating effective and well-defined protocols, methods, and devices for air disinfection. Ultraviolet (UV)-based air disinfection demonstrated promising results in inactivating viral bioaerosols. However, the reported data diversity on the required UVC doses has hindered determining the best UVC practices and led to confusion among the public and regulators. This article reviews available information on critical parameters influencing the efficacy of a UVC air disinfection system and, consequently, the required dose including the system's components as well as operational and environmental factors. There is a consensus in the literature that the interrelation of humidity and air temperature has a significant impact on the UVC susceptibility, which translate to changing the UVC efficacy of commercialized devices in indoor settings under varying conditions. Sampling and aerosolization techniques reported to have major influence on the result interpretation and it is recommended to use several sampling methods simultaneously to generate comparable and conclusive data. We also considered the safety concerns and the potential safe alternative of UVC, far-UVC. Finally, the gaps in each critical parameter and the future research needs of the field are represented. This paper is the first step to consolidating literature towards developing a standard validation protocol for UVC air disinfection devices which is determined as the one of the research needs., Competing Interests: The authors report no conflict of interest which may have influenced the discussion presented herein., (© 2022 The Authors. Published by Elsevier B.V.)

COVID-19 pandemic caused by very severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) agent is an ongoing major global health concern. The disease has caused more than 452 million affected cases and more than 6 million death worldwide. Hence, there is an urgency to search for possible medications and drug treatments. There are no approved drugs available to treat COVID-19 yet, although several vaccine candidates are already available and some of them are listed for emergency use by the world health organization (WHO). Identifying a potential drug candidate may make a significant contribution to control the expansion of COVID-19. The in vitro biological activity of asymmetric disulfides against coronavirus through the inhibition of SARS-CoV-2 main protease (Mpro) protein was reported. Due to the lack of convincing evidence those asymmetric disulfides have favorable pharmacological properties for the clinical treatment of Coronavirus, in silico evaluation should be performed to assess the potential of these compounds to inhibit the SARS-CoV-2 Mpro. In this context, we report herein the molecular docking for a series of 40 unsymmetrical aromatic disulfides as SARS-CoV-2 Mpro inhibitor. The optimal binding features of disulfides within the binding pocket of SARS-CoV-2 endoribonuclease protein (Protein Data Bank [PDB]: 6LU7) was described. Studied compounds were ranked for potential effectiveness, and those have shown high molecular docking scores were proposed as novel drug candidates against SARS-CoV-2. Moreover, the outcomes of drug similarity and ADME (Absorption, Distribution, Metabolism, and Excretion) analyses have may have the effectiveness of acting as medicines, and would be of interest as promising starting point for designing compounds against SARS-CoV-2. Finally, the stability of these three compounds in the complex with Mpro was validated through molecular dynamics (MD) simulation, in which they displayed stable trajectory and molecular properties with a consistent interaction profile., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objective: Many studies have suggested herbal medicines as alternatives or adjuvants to modern drugs for COVID-19. Their scientometric analyses can provide a scientific overview of this topic., Materials and Methods: Web of Science (WOS) and Scopus were searched for articles on the use of herbal medicines in COVID-19 published until 26 October 2020. Collected data were analyzed for document type, subject area, top journal, citation number, and authors' collaboration network using VOSviewer 1.6.15, ScientoPy 2.0.3, Gephi 0.9.2, and SPSS 15 statistical tools., Results: After screening the 3185 retrieved records, 378 and 849 records, respectively from WOS and Scopus, remained for quantity analysis. Original and review articles were the two main types of papers in both databases. Top subject areas were drug and medicine, respectively in the WOS and Scopus databases. The top three productive countries in the field were China, the US, and India. The most cited article was a practice guideline in both databases. "Journal of Biomolecular Structure Dynamics" in WOS and "Chinese Traditional and Herbal Drugs" in Scopus were the top journals. Top keywords included "COVID-19″ and "Traditional Chinese Medicine". US authors had the highest collaboration with other authors., Conclusions: The current study provides a snapshot of the quantity and characteristics of published scholarly documents in recent months in the intersection of herbal medicines and COVID-19. Our findings help scientists to find the existing gaps, identify the active authors and scientific institutes to collaborate with and use their experience to produce new knowledge in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier GmbH. All rights reserved.)

Background & Aims: The World Health Organization (WHO) HBV and HCV elimination targets, set in 2016 and based on projections to 2030, were unable to consider the impact of intervening factors. To evaluate the impact of the COVID-19 pandemic on viral hepatitis elimination programs, the European Association for the Study of the Liver (EASL) conducted a survey in liver centers worldwide in 2021., Methods: A web-based questionnaire was distributed (May-July 2021) to all EASL members representing clinical units providing HBV and HCV hepatitis care. Results are expressed as absolute numbers and reduction rates for each care activity., Results: Data were collected from 32 European and 12 non-European clinical centers. Between January 2019 (pre-pandemic) and December 2020 (during the pandemic), chronic HBV consultations decreased by 32% and 26%, new referrals by 38% and 39%, HBV testing rates by 39% and 21% (for HBsAg detection) and 30% and 22% (for HBV DNA detection), and new HBV treatments by 20% and 44% ( p  = 0.328) in European and non-European centers, respectively. With regard to HCV during the same time frame, the overall reductions were 39% and 50% for consultations, 49% and 49% for new referrals, 11% and 38% for HCV RNA detection, and 51% and 54% for new HCV antiviral treatments for European and non-European Centers, respectively ( p  = 0.071)., Conclusions: All steps in the viral hepatitis care cascade have been hampered by the COVID-19 pandemic, with a comparable impact across different centers. These data reaffirm the pandemic's major effect on global viral hepatitis elimination programs and suggest that actions to achieve the WHO 2030 targets should be reconsidered and revised to account for each country's progress relative to pre-pandemic values., Lay Summary: The EASL multinational survey conclusively shows that viral hepatitis elimination programs, expected to provide control of hepatitis B and hepatitis C worldwide by 2030, have been held back by the COVID-19 pandemic in clinical centers from several European and non-European countries, with a comparable impact across centers. Limitations in the cascade of care for both HBV and HCV were linked to limited access to screening, consultations, specific testing, and actual treatment. As restrictions for COVID-19 begin to lift, efforts to diagnose and provide treatment for viral hepatitis should remain high on the list of priorities for public health officials to maintain the WHO elimination efforts. Measures that have been put in place to control the COVID-19 pandemic could be transferred to increasing the diagnosis and linkage to care of people with hepatitis., Competing Interests: LK: Received speaker fees from Gilead and Abbvie and consultancy fees from Abbvie. MB: Received grants/research support from Abbvie, BMS, and Gilead. Received honoraria/consultation fees or participated in an advisory board for Abbvie, Gilead, GSK, Janssen, MSD, and Roche. Participated in a company-sponsored speaker’s bureau for Abbvie, Gilead, and Janssen. MRB: Received research funding from Gilead and served as a speaker for Gilead and AbbVie. MM: Nothing to declare. TB: Received grants/research support from Abbvie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Norgine, Novartis, Orphalan, and Sequana Medical. Received honoraria/consultation fees or served on the advisory board for Abbvie, Alexion, Bayer, Gilead, GSK, Eisai, Enyo Pharma, Falk Foundation, HepaRegeniX GmbH, Humedics, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Orphalan, Roche, Sequana Medical, SIRTEX, SOBI, and Shionogi. Participated in a company-sponsored speaker’s bureau for Abbvie, Alexion, Bayer, Gilead, Eisai, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, Orphalan, Sequana Medica, SIRTEX, and SOBI. FN: Advisor for Gilead and AbbVie, and received speaker fees from Roche Diagnostics. AC: Received grants and research support from AbbVie, Alfasigma, Bayer, BMS, Gilead Sciences, Intercept, MSD, and Roche. Served on advisory committees for AbbVie, Alfasigma, Bayer, BMS, Gilead Sciences, Intercept, MSD, and Roche. Participated in speaking and teaching activities for AbbVie, Alfasigma, Bayer, BMS, and Gilead Sc. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).)

Background: The presence of diabetes mellitus (DM) among COVID-19 patients is associated with increased hospitalization, morbidity, and mortality. Evidence has shown that hyperglycemia potentiates SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and plays a central role in severe COVID-19 and diabetes comorbidity. In this review, we explore the therapeutic potentials of herbal medications and natural products in the management of COVID-19 and DM comorbidity and the challenges associated with the preexisting or concurrent use of these substances., Methods: Research papers that were published from January 2016 to December 2021 were retrieved from PubMed, ScienceDirect, and Google Scholar databases. Papers reporting clinical evidence of antidiabetic activities and any available evidence of the anti-COVID-19 potential of ten selected natural products were retrieved and analyzed for discussion in this review., Results: A total of 548 papers (73 clinical trials on the antidiabetic activities of the selected natural products and 475 research and review articles on their anti-COVID-19 potential) were retrieved from the literature search for further analysis. A total of 517 articles (reviews and less relevant research papers) were excluded. A cumulative sum of thirty-one (31) research papers (20 clinical trials and 10 others) met the criteria and have been discussed in this review., Conclusion: The findings of this review suggest that phenolic compounds are the most promising phytochemicals in the management of COVID-19 and DM comorbidity. Curcumin and propolis have shown substantial evidence against COVID-19 and DM in humans and are thus, considered the best potential therapeutic options., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s). Published by Elsevier B.V.)

Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation., Objectives: We aimed to characterize the specific T-cell response on the basis of the in vitro recall of IFN-γ-producing cells to in silico -predicted peptides in samples from SARS-CoV-2 convalescent individuals., Methods: The sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4 + and CD8 + T cells. Next, we performed an in vitro recall of specific T cells from PBMC samples from the participants. The results were analyzed according to clinical features of the cohort and HLA diversity., Results: Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ-producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ-producing T cells, suggesting decreased immunity against viral peptides., Conclusion: Our data are evidence that in silico -predicted peptides are highly recognized by T cells from convalescent individuals, suggesting a possible application for vaccine design. However, the number of specific T cells decreases 180 days after infection, which might be associated with reduced protection against reinfection over time., (© 2022 The Authors.)

The current SARS-COV-2 pandemic led to a drastic drop in liver donation and transplantation in DDLT and LDLT settings. Living donations have decreased more than deceased organ donation due to the need to protect the interest of donors. In the SARS-COV-2 pandemic, major professional societies worldwide recommended against the use of organs from donors with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The basis for these recommendations are; SARS-CoV-2 could be transmitted to the recipient through organ transplantation and can result in severe manifestations; only limited effective targeted therapies are available, risk of transmission to the healthcare professionals, logistical limitations, and ethical concerns. In addition, end-stage liver disease patients on the waiting list represent vulnerable populations and are at higher risk for severe COVID-19 infection. Therefore, deferring life-saving transplants from COVID-positive donors during a pandemic may lead to more collateral damage by causing disease progression, increased death, and dropout from the waitlist. As this SARS-COV-2 pandemic is likely to stay with us for some time, we have to learn to co-exist with it. We believe that utilizing organs from mild/ asymptomatic COVID19 positive donors may expand the organ donor pool and mitigate disruptions in transplantation services during this pandemic., (© 2022 The Authors.)

Background: : Since its declaration as a global pandemic on March11 th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States., Methods: : We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019)., Results: : Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P < 0.01), higher MELD score in the recipients (25 vs 23, P <0.01), lower time on wait-list (52 vs 84 days, P <0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P =0.012), longer distance from recipient hospital (131 vs 64 miles, P <0.01) and higher donor risk index (1.65 vs 1.55, P <0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P =0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P <0.01; 92.2 vs 96.5 %, P <0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P <0.01)., Conclusions: : During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower., Competing Interests: The authors have no conflicts to declare., (© 2022 The Author(s).)

Effective treatment approaches for patients with COVID-19 remain limited and are neither curative nor widely applicable. Activated specialized tissue effector extracellular vesicles (ASTEX) derived from genetically-enhanced skin fibroblasts, exert disease-modifying bioactivity in vivo in models of heart and lung injury. Here we report that ASTEX antagonizes SARS-CoV-2 infection and its pathogenic sequelae. In human lung epithelial cells exposed to SARS-CoV-2, ASTEX is cytoprotective and antiviral. Transcriptomic analysis implicated the mammalian target of rapamycin (mTOR) pathway, as infected cells upregulated mTOR signaling and pre-exposure to ASTEX attenuated it. The implication of mTOR signaling was further confirmed using mTOR inhibition and activation, which increased and decreased viral load, respectively. Dissection of ASTEX cargo identifies miRs including miR-16 as potential inhibitors of mTOR signaling. The findings reveal a novel, dual mechanism of action for ASTEX as a therapeutic candidate for COVID-19, with synergistic antiviral and cytoprotective benefits., Competing Interests: EM owns founder stock in Capricor Therapeutics. All other authors declare no competing financial interests., (© 2022 The Authors. Published by Elsevier Ltd.)

Objective: The acute cases of pneumonia (COVID-19) were first reported from China in December 2019, and the pathogen was identified as SARS-CoV-2. Currently, many vaccines have been developed against this virus by using multiple genes, applying different platforms, and used for the vaccinations of the human population. Spike protein genes play an important role in host cell attachment and viral entry and have been extensively used for the development of vaccine and antiviral therapeutics. Short interfering RNA is also known as silencing RNA and contribute a significant role to regulate the expression of a specific gene. By using this technology, virus inhibition has been demonstrated against many viral diseases., Methods: In this work, we have reported the Insilico prediction, designing, and experimental validation of siRNAs antiviral potency against SARS-CoV-2-S-RBD. The siDirect 2.0 was selected for siRNAs prediction, and secondary structure was predicted by RNAfold while the HNADOCK was used for molecular docking analysis and specific binding of siRNAs to the selected target. We have used and evaluated four siRNAs for cellular toxicity and determination of antiviral efficiency based on the Ct value of q-real-time PCR in Vero E6 cells., Results: Based on the experimental evaluation and analysis of results from generated data, we observed that there is no cytotoxicity for any tested siRNAs in Vero E6 cells. Total four siRNA were filtered out from twenty-one siRNAs following the strict selection and scoring criteria. The better antiviral efficiency was observed in 3rd siRNAs based on the Ct value of q-real-time PCR. The results that emerged from this study encouraged us to validate the efficiency of these siRNAs in multiple cells by using alone and in a combination of two or more siRNAs to inhibit the SARS-CoV-2 proliferation., Conclusion: The Insilico prediction, molecular docking analysis provided the selection of better siRNAs. Based on the experimental evaluation only 3rd siRNA was found to be more effective than others and showed better antiviral efficiency. These siRNAs should also be evaluated in other cell lines either separately or in combination against SARS-CoV-2 to determine their antiviral efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: Uganda was affected by two major waves of coronavirus disease 2019 (COVID-19). The first wave during late 2020 and the second wave in late April 2021. This study compared epidemiologic characteristics of hospitalized (HP) and non-hospitalized patients (NHP) with COVID-19 during the two waves of COVID-19 in Uganda., Methods: Wave 1 was defined as November-December 2020, and Wave 2 was defined as April-June 2021. In total, 800 patients were included in this study. Medical record data were collected for HP (200 for each wave). Contact information was retrieved for NHP who had polymerase-chain-reaction-confirmed COVID-19 (200 for each wave) from laboratory records; these patients were interviewed by telephone., Findings: A higher proportion of HP were male in Wave 1 compared with Wave 2 (73% vs 54%; P =0.0001). More HP had severe disease or died in Wave 2 compared with Wave 1 (65% vs 31%; P <0.0001). NHP in Wave 2 were younger than those in Wave 1, but this difference was not significant (mean age 29 vs 36 years; P =0.13). HP were significantly older than NHP in Wave 2 (mean age 48 vs 29 years; P <0.0001), but not Wave 1 (mean age 48 vs 43 years; P =0.31)., Interpretation: Demographic and epidemiologic characteristics of HP and NHP differed between and within Waves 1 and 2 of COVID-19 in Uganda., (© 2022 The Author(s).)

Objective: The aim of this study was to determine current and previous SARS-COV-2 infection, and describe risk factors associated with seropositivity, among HCWs and hospital staff between June and October of 2020., Methodology: Data from the day of enrollment for a prospective cohort study were analyzed to determine point prevalence and seroprevalence of SARS-CoV-2 infection in HCWs and hospital staff of a university hospital in Colombia. Respiratory samples were collected to perform RT-PCR tests, along with blood samples to measure SARS-CoV-2 IgM and IgG antibodies. Data on nosocomial and community risk factors for infection were also collected and analyzed., Findings: 420 HCWs and hospital staff members were included. The seroprevalence at baseline was 23.2%, of which 10.7% had only IgM antibodies, 0.7% had IgG, and 11.7% had IgM and IgG. The prevalence of acute SARS-CoV-2 infection was 1.9%. Being a nurse assistant was significantly associated with seropositivity when compared with all other job duties (PR 2.39, 95% CI 1.27-3.65, p  = 0.01)., Conclusions: Overall SARS-CoV-2 prevalence was 1.9% and seroprevalence was 23.15%. Nurse assistants, medical doctors or students, and laboratory workers had a higher possibility of being SARS-CoV-2 seropositive., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Author(s).)

The mechanisms of coronavirus disease-2019 (COVID-19)-related myocardial injury comprise both direct viral invasion and indirect (hypercoagulability and immune-mediated) cellular injuries. Some patients with COVID-19 cardiac involvement have poor clinical outcomes, with preliminary data suggesting long-term structural and functional changes. These include persistent myocardial fibrosis, edema, and intraventricular thrombi with embolic events, while functionally, the left ventricle is enlarged, with a reduced ejection fraction and new-onset arrhythmias reported in a number of patients. Myocarditis post-COVID-19 vaccination is rare but more common among young male patients. Larger studies, including prospective data from biobanks, will be useful in expanding these early findings and determining their validity., Competing Interests: Dr Nazarian has received grants from the National Institutes of Health, ImriCor, Biosense Webster, and ADAS; and is a consultant to CardioSolv and ImroCor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

This review was focused on global data analysis and risk factors associated with morbidity and mortality of coronavirus disease 2019 from different countries, including Bangladesh, Brazil, China, Central Eastern Europe, Egypt, India, Iran, Pakistan, and South Asia, Africa, Turkey and UAE. Male showed higher confirmed and death cases compared to females in most of the countries. In addition, the case fatality ratio (CFR) for males was higher than for females. This gender variation in COVID-19 cases may be due to males' cultural activities, but similar variations in the number of COVID-19 affected males and females globally. Variations in the immune system can illustrate this divergent risk comparatively higher in males than females. The female immune system may have an edge to detect pathogens slightly earlier. In addition, women show comparatively higher innate and adaptive immune responses than men, which might be explained by the high density of immune-related genes in the X chromosome. Furthermore, SARS-CoV-2 viruses use angiotensin-converting enzyme 2 (ACE2) to enter the host cell, and men contain higher ACE2 than females. Therefore, males may be more vulnerable to COVID-19 than females. In addition, smoking habit also makes men susceptible to COVID-19. Considering the age-wise distribution, children and older adults were less infected than other age groups and the death rate. On the contrary, more death in the older group may be associated with less immune system function. In addition, most of these group have comorbidities like diabetes, high pressure, low lungs and kidney function, and other chronic diseases. Due to the substantial economic losses and the numerous infected people and deaths, research examining the features of the COVID-19 epidemic is essential to gain insight into mitigating its impact in the future and preparedness for any future epidemics., Competing Interests: The authors declare that they have no competing interests., (© 2022 Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated that SARS-CoV-2 is mainly transmitted by inhalation of aerosols and can remain viable in the air for hours. Viruses can spread in dental settings and put professionals and patients at high risk of infection due to proximity and aerosol-generating procedures, and poor air ventilation., Objectives: The aim of this study was to investigate the effects of a 1% hydrogen peroxide (H 2 O 2 ) mouth rinse on reducing the intraoral SARS-CoV-2 load., Methods: Portable air cleaners with HEPA filters exposed for 3 months were analysed to test for virus presence in a waiting room (where patients wore a face mask but did not undergo mouth rinsing) and three treatment rooms (where patients wore no mask but carried out mouth rinsing). As CO 2 is co-exhaled with aerosols containing SARS-CoV-2 by COVID-19 infected people, we also measured CO 2 as a proxy of infection risk indoors. Specific primer and probe RT-PCR were applied to detect viral genomes of the SARS-CoV-2 virus in the filters. Specifically, we amplified the nucleocapsid gene (Nuclv) of SARS-CoV-2., Results: CO 2 levels ranged from 860 to 907 ppm, thus indicating low ventilation and the risk of COVID-19 transmission. However, we only found viral load in filters from the waiting room and not from the treatment rooms. The results revealed the efficiency of 1-minute mouth rinsing with 1% H 2 O 2 since patients rinsed their mouths immediately after removing their mask in the treatment rooms., Conclusions: Our findings suggest that dental clinics would be safer and more COVID-19 free by implementing mouth rinsing 1 min with 1% H 2 O 2 immediately after the patients arrive at the clinic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Diabetes mellitus is a metabolic disease that causes hyperglycemia. In COVID-19 patients the severity of the disease depends on myriad factors but diabetes mellitus is the most important comorbidity. The current review was conducted to investigate the virulence of SARS-CoV-2 and disease severity of COVID-19 in type 2 diabetes mellitus patients and relevant treatment. The literature published in PubMed, Scopus, Web of Science, and Google Scholar was reviewed up to September 2021. The keywords including SARS-CoV-2, type 2 diabetes mellitus in COVID-19, hyperglycemia in COVID-19, opportunistic infections in type 2 diabetes mellitus and COVID-19 were used in different combinations. Hyperglycemic individuals over-express ACE-2 receptors in the lungs thus increasing the SARS-CoV-2 susceptibility and replication. Although dipeptidyl peptidase-4 plays an important role in glucose homeostasis, additionally it also stimulates the production of proinflammatory cytokines such as IL-6 and TNF-α creating a cytokine storm. Cytokine storm might be responsible for respiratory insufficiency in severe COVID-19 patients. Type 2 diabetes mellitus is associated with immunosuppression and the patients are prone to get many opportunistic infections. Type 2 diabetes mellitus patients with severe COVID-19 have lymphopenia. Moreover, in type 2 diabetes mellitus patients the neutrophils exhibit decreased chemotaxis, hydrogen peroxide production, and phagocytosis. Reduction in lymphocyte count and defective neutrophil capacity renders them with COVID-19 susceptible to opportunistic bacterial and fungal infections increasing the mortality rate. The opportunistic bacterial infections in COVID-19 patients were due to Staphylococcus aureus , Streptococcus pneumonia, and coagulase-negative Staphylococci, E . coli , Pseudomonas aeruginosa , and Klebsiella sp. In COVID-19 patients with type 2 diabetes mellitus, mucormycosis was found to be the most common fungal infection with a higher predilection to males. Hyperglycemia in COVID-19 patients with type 2 diabetes mellitus enhances the SARS-CoV-2 replication with an adverse outcome. A strong correlation exists between the poor prognosis of COVID-19 and type 2 diabetes mellitus. Proper glycemic control in COVID-19 patients with diabetes mellitus might lessen the severity of the disease., Competing Interests: The authors declare no conflict of interests., (© 2022 Elsevier Inc. All rights reserved.)

Exceptional pandemic lockdown measures enabled singular experiments such as analysing the energy consumption of vacant buildings. This paper assesses the impact of the COVID-19 lockdown on the energy use of academic buildings. For this purpose, weather-adjusted energy use was compared before and during the lockdown, including different levels of lockdown restrictions. Results obtained for the 83 academic buildings of Universitat Politècnica de Catalunya - Barcelona Tech (UPC) reveal that the avoided energy consumption amounted to over 4.3 GWh during the post-pandemic year. However, the results indicate that academic buildings were still using approximately 46.9% of their typical energy consumption during strict lockdown. This revelation emphasizes the high environmental burden of buildings, regardless of whether they are occupied., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: The Coronavirus disease 2019 pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the rise of many available modalities for diagnosis. One such modality is the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) kits which require evaluation amongst the many available commercial kits in the market., Methods: We conducted a performance evaluation of twelve RT-PCR SARS-CoV-2 commercial kits. A total of 75 nasopharyngeal and oropharyngeal clinical samples were selected with their cycling threshold (Ct) values. Inclusion of 5 gene targets: E gene, N gene, S gene, RdRp and ORF1ab were assessed. Data was analyzed using R software version 4.1.1 and Microsoft Excel., Results: We observe that, the positive sample's Ct values differs significantly across the 12 diagnostic kits. However, for gene-specific analysis, we observe that, positive sample's Ct values does not differ significantly across gene targets. There is significant difference in Ct values in Commercial kits targeting all genes except S-gene. All the commercial kits Altona (E and S genes), Thermo (ORF1ab and N genes), Multiplex (E, ORF1ab, RdRdp genes), Meril (N and ORF1ab genes), S D Biosensor (E and ORF1ab genes), Lab Gun (RdRp and N genes) and Lab systems (ORF1ab and E genes) scored a sensitivity of 100%. All other kits scored sensitivity above 95% and lowest sensitivity with the Genes2me (E gene) and Genes2me (RdRp) at 95.08% each. All kits were 100% specific., Conclusion: This study provides an accurate comprehensive assessment of the different kits in the detection of SARS-CoV-2 which may promote standardization of testing across laboratories., Competing Interests: The author(s) declare that there are no conflicts of interest, (© 2021 The Author(s).)

The COVID-19 pandemic has caused mayhem globally since the beginning of 2020. Owing to the immune dysfunction inherent to cirrhosis and the poor general condition, patients with chronic liver disease (CLD) are at higher risk of mortality and morbidity due to COVID-19. Recently, a number of vaccines against SARS-Cov-2 have been approved for emergency use around the globe. Although the phase 2/3 trials of these vaccines show them to be safe and effective in the general population, data in patients with CLD are scarce. The number of patients with CLD enrolled on these trials is small, and no liver-related adverse effects have been reported yet. Various liver societies have come up with guidelines on vaccination in this population and recommend vaccination on a priority basis. Trials to assess the safety and efficacy of the COVID vaccines are underway and are likely to provide valuable insight into this matter., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Tremendous progress has been made in the treatment of ST-segment elevation myocardial infarction (STEMI), the most severe and time-sensitive acute coronary syndrome. Primary percutaneous coronary intervention (PCI) is the preferred method of reperfusion, which has stimulated the development of regional STEMI systems of care with standardized protocols designed to optimize care. However, challenges remain for patients with cardiogenic shock, out-of-hospital cardiac arrest, an expected delay to reperfusion (>120 min), in-hospital STEMI, and more recently, those with Covid-19 infection. Ultimately, the goal is to provide timely reperfusion with primary PCI coupled with the optimal antiplatelet and anticoagulant therapies. We review the challenges and provide insights into the remaining knowledge gaps for contemporary STEMI care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality., Methods: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk., Findings: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% ( n  = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p  = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p =  0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p =  0.015., Interpretation: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk., Funding: No funding was obtained for this study., Competing Interests: Dr. Tignanelli has a relationship (contract/grant) with the Gates Foundation and Minnesota Partnerships to conduct randomized controlled trial(s) of Losartan in COVID-19, outside the submitted work. Dr. Haslbauer and Dr. Tzankov received funding support from the Botnar Research Centre for Child Health Foundation Research Grant on COVID-19 for all their COVID-19 related research, outside the submitted research. Dr. Lutsey received NIH grants outside the submitted work. Dr. Shah received a MHealth Fairview Learning health system K12 grant, travel award for HTRS colloquium and ASH Medical educator institute award, and has a ASH system-based hematology committee leadership role. All theother authors have nothing to disclose, (© 2021 The Authors.)

SARS-CoV-2-specific IgM antibodies wane during the first three months after infection and IgG antibody levels decline. This may limit the ability of antibody tests to identify previous SARS-CoV-2 infection at later time points. To examine if the diagnostic sensitivity of antibody tests falls off, we compared the sensitivity of two nucleoprotein-based antibody tests, the Roche Elecsis II Anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay and three glycoprotein-based tests, the Abbott SARS-CoV-2 IgG II Quant, Siemens Atellica IM COV2T and Euroimmun SARS-CoV-2 assay with 53 sera obtained 6 months after SARS-CoV-2 infection. The sensitivity of the Roche, Abbott SARS-CoV-2 IgG II Quant and Siemens antibody assays was 94.3% (95% confidence interval (CI) 84.3-98.8%), 98.1 % (95% CI: 89.9-100%) and 100 % (95% CI: 93.3-100%). The sensitivity of the N-based Abbott SARS-CoV-2 IgG and the glycoprotein-based Euroimmun ELISA was 45.3 % (95% CI: 31.6-59.6%) and 83.3% (95% CI: 70.2-91.9%). The nucleoprotein-based Roche and the glycoprotein-based Abbott receptor binding domain (RBD) and Siemens tests were more sensitive than the N-based Abbott and the Euroimmun antibody tests ( p  = 0.0001 to p  = 0.039). The N-based Abbott antibody test was less sensitive 6 months than 4-10 weeks after SARS-CoV-2 infection ( p  = 0.0001). The findings show that most SARS-CoV-2 antibody assays correctly identified previous infection 6 months after infection. The sensitivity of pan-Ig antibody tests was not reduced at 6 months when IgM antibodies have usually disappeared. However, one of the nucleoprotein-based antibody tests significantly lost diagnostic sensitivity over time., Competing Interests: The authors declare that there are no conflicts of interests., (© 2021 The Author(s).)

In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS-Cov, and SARS-Cov. Moreover, researchers are scrambling to identify novel drug targets and discover novel therapeutic options to vanquish the current pandemic. Since there is no definitive treatment to control Covid-19 vaccines are remain to be a lifeline. Currently, many vaccine candidates are being developed with most of them are reported to have positive results. Therapeutic targets such as helicases, transmembrane serine protease 2, cathepsin L, cyclin G-associated kinase, adaptor-associated kinase 1, two-pore channel, viral virulence factors, 3-chymotrypsin-like protease, suppression of excessive inflammatory response, inhibition of viral membrane, nucleocapsid, envelope, and accessory proteins, and inhibition of endocytosis were identified as a potential target against COVID-19 infection. This review also summarizes plant-based medicines for the treatment of COVID-19 such as saposhnikoviae divaricata, lonicerae japonicae flos, scutellaria baicalensis, lonicera japonicae, and some others. Thus, this review aimed to focus on the most promising therapeutic targets being repurposed against COVID-19 and viral elements that are used in COVID-19 vaccine candidates., Competing Interests: The authors declare that they have no competing interests., (© 2021 Published by Elsevier Inc.)

The fast spread of SARS-CoV-2 presented a worldwide challenge to public health, economy, and educational system, affecting wellbeing of human society. With high transmission rates, there are increasing evidences of COVID-19 spread via bioaerosols from an infected person. The current review was conducted to examine airborne pollen impact on COVID-19 transmission and to identify the major gaps for post-pandemic research. The study used all key terms to identify revenant literature and observation were collated for the current research. Based on existing literature, there is a potential association between pollen bioaerosols and COVID-19. There are few studies focusing the impact of airborne pollen on SARS-CoV-2, which could be useful to advance future research. Allergic rhinitis and asthma patients were found to have pre-modified immune activation, which could help to provide protection against COVID-19. However, does airborne pollen acts as a potent carrier for SARS-CoV-2 transport, dispersal and its proliferation still require multidisciplinary research. Further, a clear conclusion cannot be drawn due to limited evidence and hence more research is needed to show how pollen bioaerosols could affect virus survivals. The small but growing literature review focuses on searching for every possible answer to provide additional security layers to overcome near future corona-like infectious diseases., Competing Interests: The authors report no declarations of interest., (© 2021 Elsevier Ltd. All rights reserved.)

Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic., Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave., Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37)., Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making., Lay Summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes., Competing Interests: SM.-M.: Speaker fees from Bayer and travel funding from 10.13039/100004326Bayer and 10.13039/501100014382Eisai. V.S.: Travel grants from 10.13039/100004326Bayer. A.F.: Lecture fees from Bayer, Gilead and MSD; consultancy fees from Bayer, AstraZeneca, Roche and Guerbert. J-C.N.: Received research grant from 10.13039/100004326Bayer for Inserm UMR1138. L.R.: Reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO BioSciences, 10.13039/100004325AstraZeneca, BeiGene, 10.13039/501100003769Eisai, 10.13039/100010544Exelixis, 10.13039/100006591Fibrogen, Incyte, 10.13039/501100014382Ipsen, 10.13039/100004312Lilly, 10.13039/100007054MSD, 10.13039/100004337Roche. B.S.: Reports consultancy fees from Adaptimmune, AstraZeneca, Bayer, BMS, BTG, Eli Lilly, Ipsen, Novartis, Merck, Roche, Sirtex Medical, Terumo; and research grants from 10.13039/100002491BMS and Sirtex Medical. J. Bruix: Consultancy: AbbVie, ArQule, Astra, Basilea, Bayer, BMS, Daiichi Sankyo, GlaxoSmithKline, Gilead, Kowa, Lilly, Medimune, Novartis, Onxeo, Polaris, Quirem, Roche, Sanofi-Aventis, Sirtex, Terumo/Grants: 10.13039/100004326Bayer and 10.13039/501100014382Ipsen. M.S.Z.: Received speaker fees and travel grants from 10.13039/100004326Bayer and 10.13039/100014869BTG, 10.13039/100007054MSD. M.B.: Consultant and Advisory Board for: Bayer Pharma, Ipsen, BMS, Eisai, Roche, AstraZeneca, Sirtex Medical. D.J.P.: Received lecture fees from ViiV Healthcare and Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and AstraZeneca; received research funding (to institution) from MSD and BMS. T.M.: Consultancy: Eisai, Roche, BTG, Ipsen, Bayer, Adaptimmune. Research funding: Bayer, BTG. H.W.: Served as speaker for Bayer, Eisai, and Ipsen, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche, and Ipsen. B.M.: Consultancy: Bayer-Shering Pharma /Speaker fees: Eisai, MSDG. C. Consultancy fees from Bayer, Ipsen. P.R.G.: Bayer, BMS, MSD, AstraZeneca, Adaptimmune, Sirtex, Lilly Ipsen, Roche, Eisai. M.R.A.S.: Has received Research grants, advisory board or speaker fees for 10.13039/100006483AbbVie, 10.13039/100004326Bayer, Biolab, Intercept, 10.13039/501100014382Ipsen, 10.13039/100008799Gilead, 10.13039/100009947MSD, 10.13039/100004336Novartis, and 10.13039/100004337Roche. J.T.: Has received research grants from 10.13039/100004337Roche and 10.13039/501100014382Ipsen. He has received speaker and consulting honoraria from AstraZeneca, Amgen, Bayer Healthcare, Bristol Myers-Squibb, Eisai, Ipsen, Merck Serono, Merck Sharp & Dome, Lilly Imclone, and Roche. J. Bridgewater: Consultancy Bayer, BMS, Incyte, Taiho, Roche, MSD and Merck Serono. Research funding from Incyte. G.C.: Consultancy fees from Bayer, Ipsen. A.L.: Consultancy CAScination, Advisory Board Neuwave and Histosonics. H.T.: Speaker fees from AbbVie, Gilead, MSD, and Bayer. R.V.: Research grant from 10.13039/100006483Abbvie. A.M.M.P.: Speaker honorarium from Bayer, BMS, Boston Scientific and EISAI. Consulting honorarium from Bayer, AstraZeneca and EISAI. Advisory honorarium from Bayer, AstraZeneca and EISAI. Grants from 10.13039/100004326Bayer and 10.13039/100008497Boston Scientific. M.D.: Has received consulting and training fees from Bayer and Eisai. B.B.: Reports Consultancy for GenMab (paid to Institution); Advisory Boards for Roche (paid to Institution), Eisai Europe Limited (paid to Institution), research grant from 10.13039/100006436Celgene Ltd (paid to Institution), Speakers Bureau for Eisai Europe Limited (paid to Institution), Travel and registration for Congress from Bayer. L.d.F.: Lectures fees from BMS, Roche and Bayer. B.M.M.: Advisory/Speaker: Amgen, AstraZeneca, Bayer, BMS, Eisai, Ipsen, Merck, Roche, Sanoffi Genzyme, Taiho. Expert Testimony: Eisai, Roche. Travel: Eisai, Merck. Research: Sillajen (Individual); AstraZeneca, H3/Eisai, Galera, GSK, Exelixis (Institution). M.S.: Travel/ accommodation/meeting expenses: Bayer. Eisai. Speaker fees: Bayer. C.R.L.: Travel grants from 10.13039/100004326Bayer. M.R-G.: Reports grants from Intercept, grants from 10.13039/100005564Gilead-Sciences, personal fees from Shionogi, personal fees from Alfa-Wasserman, personal fees from Prosciento, personal fees from Kaleido, personal fees from Novonrdisk, personal fees from MSD, personal fees from BMS, personal fees from Allergan, personal fees from Boehriger-Ingelheim, personal fees from Zydus, personal fees from Intercept Pharma, personal fees from Gilead-Sciences, outside the submitted work. F.P.: Disclosures: Received speaker honoraria from Bayer, Roche, LKM-Biotoscana, RAFFO. Research Grants from INC Argentinean 10.13039/100013137National Institute of Corrections, 10.13039/100004337Roche. V.M.: Lectures sponsored by Bayer. G.B.: Advisory board Eli-Lilly and Incyte. M. Vergara: Travel grants from 10.13039/100004326Bayer, 10.13039/100008799Gilead, 10.13039/100009947MSD and 10.13039/100006483Abbvie. Lectures sponsored by Gilead, Abbvie, Intercept, and MSD. M.L.: Lectures and educational presentations: Abbvie. Travel/accommodation, meeting expenses covered by Bayer, Gilead, Abbvie. M.I.: Received speaker honoraria from Bayer, Gilead Sciences, BMS, Janssen, Ipsen, MSD, BTG-Boston Scientific, AbbVie, EISAI, and was consultant for BTG-Boston Scientific, Bayer, and Guerbet. M.R.: Consultancy: Bayer-Schering Pharma, BMS, Roche, Ipsen, AstraZeneca, Lilly, BTG/Paid conferences: Bayer-Schering Pharma, BMS, Gilead, Lilly/Research Grants: 10.13039/100004326Bayer-Schering Pharma, 10.13039/501100014382Ipsen. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Viruses are biologically active parasites that only exist inside a host they are submicroscopic level. The novel coronavirus disease, or COVID-19, is generally caused by the SARS-CoV-2 virus and is comparable to severe acute respiratory syndrome (SARS). As a result of globalization, natural alterations or changes in the SARS-CoV-2 have created significant risks to human health over time. These viruses can live and survive in different ways in the atmosphere unless they reach another host body. At this stage, we will discuss the details of the transmission and detection of this deadly SARS-CoV-2 virus via certain environmental media, such as the atmosphere, water, air, sewage water, soil, temperature, relative humidity, and bioaerosol, to better understand the diffusion, survival, infection potential and diagnosis of COVID-19., Competing Interests: The authors declare that they have no competing interests., (© 2021 Published by Elsevier B.V.)

The ongoing mutations in the structural proteins of SARS-CoV-2 are the major impediment for prevention and control of the COVID-19 disease. Presently we focused on evolution of the envelope (E) protein, one of the most enigmatic and less studied protein among the four structural proteins (S, E, M and N) associated with multitude of immunopathological functions of SARS-CoV-2. In the present study, we comprehensively analyzed 81,818 high quality E protein sequences of SARS-CoV-2 globally available in the GISAID database as of 20 August 2020. Compared to Wuhan reference strain, our mutational analysis explored only 1.2 % (982/81818) mutant strains undergoing a total of 115 unique amino acid (aa) substitutions in the E protein, highlighting the fact that most (98.8 %) of the E protein of SARS-CoV-2 strains are highly conserved. Moreover, we found 58.77 % (134 of 228) nucleotides (nt) positions of SARS-CoV-2 E gene encountering a total of 176 unique nt-level mutations globally, which may affect the efficacy of real time RT-PCR-based molecular detection of COVID-19. Importantly, higher aa variations observed in the C-terminal domain (CTD) of the E protein, particularly at Ser 55 -Phe 56 , Arg 69 and the C-terminal end (DLLV: 72-75) may alter the binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 and thus could play a key role in COVID-19 pathogenesis. Furthermore, this study revealed the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. Our analysis also observed a triple cysteine motif harboring mutation (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of the structural proteins including the envelope protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing., Competing Interests: The authors declare no conflict of interests., (© 2020 Elsevier Inc. All rights reserved.)

The current life-threatening and tenacious pandemic eruption of coronavirus disease in 2019 (COVID-19) has posed a significant global hazard concerning high mortality rate, economic meltdown, and everyday life distress. The rapid spread of COVID-19 demands countermeasures to combat this deadly virus. Currently, there are no drugs approved by the FDA to treat COVID-19. Therefore, discovering small molecule therapeutics for treating COVID-19 infection is essential. So far, only a few small molecule inhibitors are reported for coronaviruses. There is a need to expand the small chemical space of coronaviruses inhibitors by adding potent and selective scaffolds with anti-COVID activity. In this context, the huge antiviral chemical space already available can be analysed using cheminformatic and machine learning to unearth new scaffolds. We created three specific datasets called "antiviral dataset" (N = 38,428) "drug-like antiviral dataset" (N = 20,963) and "anticorona dataset" (N = 433) for this purpose. We analyzed the 433 molecules of "anticorona dataset" for their scaffold diversity, physicochemical distributions, principal component analysis, activity cliffs, R-group decomposition, and scaffold mapping. The scaffold diversity of the "anticorona dataset" in terms of Murcko scaffold analysis demonstrates a thorough representation of diverse chemical scaffolds. However, physicochemical descriptor analysis and principal component analysis demonstrated negligible drug-like features for the "anticorona dataset" molecules. The "antiviral dataset" and "drug-like antiviral dataset" showed low scaffold diversity as measured by the Gini coefficient. The hierarchical clustering of the "antiviral dataset" against the "anticorona dataset" demonstrated little molecular similarity. We generated a library of frequent fragments and polypharmacological ligands targeting various essential viral proteins such as main protease, helicase, papain-like protease, and replicase polyprotein 1ab. Further structural and chemical features of the "anticorona dataset" were compared with SARS-CoV-2 repurposed drugs, FDA-approved drugs, natural products, and drugs currently in clinical trials. Using machine learning tool DCA (DMax Chemistry Assistant), we converted the "anticorona dataset" into an elegant hypothesis with significant functional biological relevance. Machine learning analysis uncovered that FDA approved drugs, Tizanidine HCl, Cefazolin, Raltegravir, Azilsartan, Acalabrutinib, Luliconazole, Sitagliptin, Meloxicam (Mobic), Succinyl sulfathiazole, Fluconazole, and Pranlukast could be repurposed as effective drugs for COVID-19. Fragment-based scaffold analysis and R-group decomposition uncovered pyrrolidine and the indole molecular scaffolds as the potent fragments for designing and synthesizing the novel drug-like molecules for targeting SARS-CoV-2. This comprehensive and systematic assessment of small-molecule viral therapeutics' entire chemical space realised critical insights to potentially privileged scaffolds that could aid in enrichment and rapid discovery of efficacious antiviral drugs for COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (M pro /3CL pro ) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

The coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by an RNA virus termed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 possesses an almost 30kbp long genome. The genome contains open-reading frame 1ab (ORF1ab) gene, the largest one of SARS-CoV-2, encoding polyprotein PP1ab and PP1a responsible for viral transcription and replication. Several vaccines have already been approved by the respective authorities over the world to develop herd immunity among the population. In consonance with this effort, RNA interference (RNAi) technology holds the possibility to strengthen the fight against this virus. Here, we have implemented a computational approach to predict potential short interfering RNAs including small interfering RNAs (siRNAs) and microRNAs (miRNAs), which are presumed to be intrinsically active against SARS-CoV-2. In doing so, we have screened miRNA library and siRNA library targeting the ORF1ab gene. We predicted the potential miRNA and siRNA candidate molecules utilizing an array of bioinformatic tools. By extending the analysis, out of 24 potential pre-miRNA hairpins and 131 siRNAs, 12 human miRNA and 10 siRNA molecules were sorted as potential therapeutic agents against SARS-CoV-2 based on their GC content, melting temperature (T m ), heat capacity (C p ), hybridization and minimal free energy (MFE) of hybridization. This computational study is focused on lessening the extensive time and labor needed in conventional trial and error based wet lab methods and it has the potential to act as a decent base for future researchers to develop a successful RNAi therapeutic., Competing Interests: The authors declare no conflict of interest among them., (© 2021 The Author(s).)

Background: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2., Methods: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information., Findings: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss ( p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss ( p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level ( p value <0.05)., Interpretation: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2., Funding: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This paper has never been published elsewhere., (© 2020 The Authors.)