Study of SARS-nCoV2 Indian Isolates Gaining Insights into Mutation Fre-quencies, Protein Stability and Prospective Effect on Pathogenicity

Background: SARS-nCOV-2 is a variant of the known SARS coronavirus family. The mutations in viruses are very rapid and can play a crucial role in the evolution or devolution of the organism. This has a direct impact on "host jumping" and the pathogenicity of the virus. Objective(s): The study aims to understand the frequency of genomic variations that have occurred in the virus affecting the Indian sub-population. The impact of variations translating to proteins and its consequences affecting protein stability and interaction were studied. Method(s): Phylogenetic analysis of the 140 genomes from the India region was performed, followed by SNP and Indel analysis of both CDS and non-CDS regions. This effort was followed by a prediction of mutations occurring in 8 proteins of interest and the impact on protein stability and prospective drug interactions. Result(s): Genomes showed variability in origin, and major branches can be mapped to the 2002 outbreak of SARS. The mutation frequency in CDS regions showed that 241 C >T, 3037 C >T, 2836 C >T, and 6312 C >A occurred in 81.5% of genomes mapping to major genes. Corresponding mutations were mapped to protein sequences. The effect of mutations occurring in spike glycoprotein, RNA dependent RNA polymerase, nsp8, nucleocapsid and 3c protease was also depicted. Conclusion(s): Whilst the mutations in spike glycoprotein showcased an increase in protein stability, the residues undergoing mutations were also a part of drug binding pockets for hydroxychloro-quine. Mutations occurring in other proteins of interest led to a decrease in protein stability. The mutations were also a part of drug binding pockets for Favipiravir, Remdesivir and Dexametha-sone. The work allows analyzing larger datasets to understand mutation patterns globally.Copyright © 2021 Bentham Science Publishers.

Computational Prediction of Cassia angustifolia Compounds as a potential Drug Agents against Main Protease of SARS-nCov2

Background: In November-December 2019, a plethora of pneumonia like cases were reported in Wuhan, China. After some time, the causative agent of this ailment was identified and named as a novel coronavirus 2. This novel virus spread over the world with no time and declared as pandemic by WHO. To develop antiviral drugs, different clinically used drugs were used as a trial but went in vain. In the current study, we choose an herb with already known therapeutic effects to check its antiviral properties against this virus too. Methods: Cassia angustifolia is a well-known herb for pharmaceutical industries as its different compounds are already used in different medicines. Here we performed molecular docking of main compounds of Cassia angustifolia against the main protease of SARS-nCoV2 and were compared with different drugs that are already being used on commercial bases to obtain the lowest energy complex. Auto-Dock vina and its packages were used for molecular docking of SARS-nCov2. Results: Molecular docking of Cassia angustifolia compounds represent very promising binding energies complexes, e.g., Sennoside B gives -9.05kcal/mol and Aloe-Emodin give -4 Kcal/mol of energy against the main protease of coronavirus. In contrast, a couple of commercially used antiviral drugs were also evaluated against the selected protein of coronavirus e.g., Hydroxychloroquine and Ribavirin complexes appeared with -5.2 Kcal/mol and -6.3 Kcal/mol of energy respectively. Conclusion: Many compounds of Cassia angustifolia showed the promising energy complexes even better than the commercially used antiviral drugs e.g., Sennoside B which has the best energies against main protease of coronavirus. Further, in-vivo and in-vitro studies are needed to validate this hypothesis with advanced MD simulations and wet-lab experimentations.

Synthesis, crystal structure, DFT and molecular docking studies of N-acetyl-2,4-[diaryl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazoles: A potential SARS-nCoV-2 Mpro (COVID-19) inhibitor.

In this paper, we describe the synthesis and crystal structure analysis of N-acetyl-2,4-[diphenyl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazole (3a) and N-acetyl- 2,4-[bis(p-methoxyphenyl)-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazole (3b). The title compounds 3a and 3b are characterized by 1D NMR and single crystal x-ray diffraction analysis. Non-covalent interactions in a molecule were identified by Hirshfeld surface (dnorm contacts and 2D fingerprint plot) analysis. In addition, the existence of chalcogen bond (S•••O bond) in the molecular structures (3a and 3b) are described by NCI-RDG and QTAIM analysis. NBO analysis is employed to describe the orbital interactions and electron transfer between sulfur and oxygen atoms. Molecular docking is carried out for compounds 3a and 3b with COVID-19 viral protein SARS-nCoV-2 Mpro (PDB ID: 6LU7).

Potential risk factors associated with COVID-19 in health care workers.

BACKGROUND: Health care workers (HCWs) have been recognized as being at higher risk for coronavirus disease 2019 (COVID-19) infection; however, relevant factors and magnitude have not been clearly elucidated. AIM: This study was aimed to describe COVID-19 infections among hospital employees at a large tertiary care hospital located in Ontario, Canada from March to July 2020, towards better understanding potential risk factors. METHODS: Data on all HCWs with either a positive COVID test or a high-risk exposure from March to July 2020 were analyzed. HCWs with positive COVID test results and high-risk exposures were described. Those who developed COVID-19 following high-risk exposure were compared to those who did not. Data were also analyzed to determine trends over time. RESULTS: Over the period of observation, 193 staff (2% of total working staff) had a positive COVID-19 test. Incidence of HCW infections closely followed community incidence. Overall, 31% of COVID-19 cases were deemed occupationally acquired. Of these, 41% were acquired from a patient, with the remainder (59%) from fellow staff. Over the same period, 204 staff were identified as having a high-risk exposure. The majority of exposures (55%) were patient-associated, with the remaining (45%) resulting from staff-to-staff contact. Overall, 13% went on to develop COVID-19. Of these cases, 58% were patient-associated and 42% were a result of staff-to-staff transmission. CONCLUSIONS: HCWs are at risk for work-related COVID-19. Given the number of infections attributed to staff-staff transmission, greater attention could be paid to implementing prevention measures in non-clinical areas.

Protocol for a systematic review and meta-analysis of observational studies examining the impact of COVID-19 safety measures on physical activity patterns in adults.

BACKGROUND: The primary objective of this study is twofold: (1) to examine the effect of COVID-19 safety measures, enacted to prevent transmission of SARS-nCOV-2, on total physical activity in the adult general population (≥ 18 years) and (2) to analyze the impact of the factor "severity of safety measures" on potential changes in physical activity. The secondary objective is to investigate the effects of safety measures on the respective PA intensities, i.e., sedentary behavior, light, moderate, and vigorous physical activity. METHODS: A systematic literature search will be performed in the following online databases: Medline (on Ovid), Web of Science, Scopus, L.OVE Coronavirus disease by Epistemonikos, and ProQuest Dissertations & Theses A&I. All obtained citations will undergo title and abstract as well as full-text screening by two independent reviewers. Observational studies investigating the effects of safety measures on physical activity patterns in the adult general population will be included. The standardized mean difference in total physical activity per time unit between pre- and during COVID-19 or between normative data and during COVID-19 will be the primary outcome. The standardized mean difference in sedentary time, light, moderate, and vigorous physical activity will be assessed as secondary outcomes. Eligible studies will be divided between the reviewers for data extraction using a pilot-tested data form. Risk of bias assessment will be performed using a standard assessment tool. If suitable, a random-effects meta-analysis and meta-regression with a unit of safety measure severity as the independent variable will be performed. DISCUSSION: This study will synthesize available data reporting the effect of COVID-19 safety measures on physical activity patterns in adults. Furthermore, we will incorporate a unit for the severity of safety measures for better generalizability of the results. These findings will be of great value for public health policymaking and estimating future health consequences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021231039.

Role of Information Technology in COVID-19 Vaccination Drive: An Analysis of the COVID-19 Global Beliefs, Behaviors, and Norms Survey.

With the onset of the COVID-19 pandemic, information technology has played a critical role in healthcare. A broad spectrum of information technology tools and applications played an essential role to create awareness of the COVID-19 vaccination drive and its health benefits. Research conducted by Massachusetts Institute of Technology (MIT) in collaboration with information technology platforms like Facebook with inputs from World Health Organization (WHO), John Hopkins University (JHU), and Global Outbreak Alert and Response Network (GOARN) shows that 65.06% of people all over the globe are willing to get vaccinated. Vaccine acceptance depends upon social norms and human behavior. These organizations conducted the global survey in over 60 countries with a sample size of 437,236 responses. The international survey was organized using a pre-registered randomized experiment demonstrating the role of technology in reaching out to people based in diverse communities and evaluating their beliefs, behavior, and social norms. The study shows that vaccine acceptance can vary due to descriptive norms. All the respondents in the study were adults with access to the internet. Moreover, a large proportion of the population thinks that the COVID-19 pandemic is a viable threat to the community and preventive measures need to be taken including vaccination drives to eradicate the menace. The survey consisted of five blocks involving questions related to healthcare, demographics, vaccines, knowledge, and information exposure. Sampling and weighting were done using a pool of 3,000 respondents over two weeks, and weights were provided per respondent to represent the target population as a whole. It reduces the representation error and minimizes non-response biases.

Whole genome comparison of Pakistani Corona virus with Chinese and US Strains along with its predictive severity of COVID-19.

Initially submitted 784 SARS-nCoV2 whole genome sequences on NCBI Virus database were selected for phylogenetic analysis to look into their similarities with two of Pakistani sequenced coronavirus strains having accessions of MT240479 and MT262993. The MT240479 named (Gilgit1-Pak) was found in close proximity to MT184913 named (CruiseA-USA), while MT262993 named (Manga-Pak) was in neighboring to MT039887 named (WI-USA) strain, which were further chosen for variant calling analysis along with reference genome NC_045512 as out-group to construct concluding cladogram and looked for evolutionary distance with PAUP software in this article. Aforementioned Pakistani strains each of having 29,836 bases were compared with MT263429 (WI-USA) of 29,889 bases and MT259229 (Wuhan-P.R. China) of 29,864 bases. Whole genome variant calling pipeline revealed 31 variants in both Pakistani strains collectively (Manga-Pak vs USA having 2del & 7SNPs, while different from Chinese strain with 2del & 2SNPs, similarly Gilgit1-Pak vs USA having 10SNPs, while different from Chinese strains having 8SNPs). These variants harbour ORF1ab, ORF1a and N genes having their role is viral replication/translation, host innate immunity and viral capsid formation respectively. These novel variants may be one of the reasons for low mortality rate in Pakistan with 385 deaths as compared to USA with 63,871 and P.R. China with 4633 by May 01, 2020. However functional characterization of these variants and their integrations with other viral proteins including variability of human receptors (ACE2 & NRP1) may be the other reasons for unlikely COVID-19 statistics in Pakistan which need further confirmatory studies. Moreover, mutated N and ORF1a proteins in Pakistani strains were also analyzed by 3D structure modeling, which give another dimension of comparing these alterations at amino acid level. In a nutshell, these novel variants are correlated with reduced mortality of COVID-19 severity in Pakistan while more robust results can be obtained by wet lab experimentation. This also gives insight of genomic landscape of these indigenous strains to develop diagnostics kits, vaccines and therapeutic interventions.

An Analysis of the Generalizability and Stability of the Halo Effect During the COVID-19 Pandemic Outbreak.

The influence on the global evaluation of a person based on the perception of a single trait is a phenomenon widely investigated in social psychology. Widely regarded as Halo effect, this phenomenon has been studied for more than 100 years now, and findings such as the relationship between aesthetic perception and other personality traits-such as competence and trustworthiness-have since been uncovered. Trustworthiness plays an especially crucial role in individuals' social interactions. Despite the large body of literature published on the Halo effect, and especially on the relationship between aesthetic appearance and perceived trustworthiness, little is known about the overall generalizability of the effect, as almost all of the studies have been conducted on adult participants from Western countries. Moreover, little is known about the stability of the effect over time, in the event of major destabilization, such as the outbreak of a pandemic. In this work, the cross-cultural generalizability of the Halo effect is investigated before and during the first few months of the COVID-19 pandemic. An analysis of the generalizability and stability over time of the Halo effect is presented. Participants (N = 380, N = 145 Asians, N = 235 Caucasians) have been asked to rate the aesthetic appearance and perceived trustworthiness of a set of human faces of different ages, gender, and ethnicity. Result of our analysis demonstrated that the Halo effect (Aesthetic × trustworthiness) is influenced by the age of presented faces, but not by their gender or ethnicity. Moreover, our results show that the strength of the effect can be affected by external events and that the volatility is higher for adults' than children's faces.

Endoscopy in Otorhinolaryngology During Corona Outbreak: A Proposal for Safe Practice.

Coronavirus disease 2019 (COVID-19) is a type of viral pneumonia that has paralysed the entire world both in terms of health and economy. It has been recently declared as a global pandemic. All the health care professionals must be aware of the disease entity and take precautionary measures to control its transmission from person to person, particularly in hospital settings. In this article, we propose essential steps that can be implemented at the departmental and institutional levels to do endoscopic diagnostic procedures effectively during COVID-19 outbreak and to break the transmission chain.

Structure-based virtual screening, molecular dynamics and binding affinity calculations of some potential phytocompounds against SARS-CoV-2.

COVID-19 caused by a positive-sense single stranded RNA virus named as severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) triggered the global pandemic. This virus has infected about 10.37 Crores and taken lives of 2.24 Crores people of 213 countries to date. To cope-up this emergency clinical trials are undergoing with some existing drugs like remdesivir, flavipiravir, lopinavir-ritonavir, nafamostat, doxycycline, hydroxy-chloroquine, dexamethasone, etc., despite their severe toxicity and health hazards among diabetics, hypertensive, cardiac patients or normal individuals. The lack of safe and approved treatment for COVID-19 has forced the scientific community to find novel and safe compounds with potential efficacy. This study evaluates a few selective herbal compounds like glucoraphanin, vitexin, niazinin, etc., as a potential inhibitor of the spike protein and 3-chymotrypsin-like protease (3CLpro) or main protease (Mpro) of SARS-COV-2 through in-silico virtual studies such as molecular docking, target analysis, toxicity prediction and ADME prediction and supported by a Molecular-Dynamic simulation. Selective phytocompounds were docked successfully in the binding site of spike glycoprotein and 3CLpro (Mpro) of SARS-CoV-2. In-silico approaches also predict this molecule to have good solubility, pharmacodynamic property and target accuracy through MD simulation and ADME studies. These hit molecules niazinin, vitexin, glucoraphanin also obey Lipinski's rule along with their stable binding towards target protein of the virus, which makes them suitable for further biochemical and cell-based assays followed by clinical investigations to highlight their potential use in COVID-19 treatment.Communicated by Ramaswamy H. Sarma.

Estimation of parameters for a humidity-dependent compartmental model of the COVID-19 outbreak.

Building an effective and highly usable epidemiology model presents two main challenges: finding the appropriate, realistic enough model that takes into account complex biological, social and environmental parameters and efficiently estimating the parameter values with which the model can accurately match the available outbreak data, provide useful projections. The reproduction number of the novel coronavirus (SARS-CoV-2) has been found to vary over time, potentially being influenced by a multitude of factors such as varying control strategies, changes in public awareness and reaction or, as a recent study suggests, sensitivity to temperature or humidity changes. To take into consideration these constantly evolving factors, the paper introduces a time dynamic, humidity-dependent SEIR-type extended epidemiological model with range-defined parameters. Using primarily the historical data of the outbreak from Northern and Southern Italy and with the help of stochastic global optimization algorithms, we are able to determine a model parameter estimation that provides a high-quality fit to the data. The time-dependent contact rate showed a quick drop to a value slightly below 2. Applying the model for the COVID-19 outbreak in the northern region of Italy, we obtained parameters that suggest a slower shrinkage of the contact rate to a value slightly above 4. These findings indicate that model fitting and validation, even on a limited amount of available data, can provide useful insights and projections, uncover aspects that upon improvement might help mitigate the disease spreading.

Peptides-based vaccine against SARS-nCoV-2 antigenic fragmented synthetic epitopes recognized by T cell and ß-cell initiation of specific antibodies to fight the infection.

The World Health Organization has declared the rapidly spreading coronavirus to be a global pandemic. The FDA is yet to approve a vaccine for human novel coronavirus. Here, we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell- and ß-cell-recognized epitopes for producing specific antibodies against SARS-nCoV-2. We construct ~ 12 P' antigenic epitope peptides to develop a more effective vaccine and identify specific antibodies. These epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding affinity. All antigens identified of SARS-nCoV-2 different proteins by each attached specific ~ 1-7 L linker adaptor were used to construct a broad single peripheral peptide vaccine. It is expected to be highly antigenic with a minimum allergic effect. As a result of these exciting outcomes, expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and ß-cells. An in vitro study for the proposed peptide-based vaccine is mostly recommended. Further clinical trials are required to check the efficacy of this vaccine.

Unusual association of COVID-19, pulmonary tuberculosis and human immunodeficiency virus, having progressed favorably under treatment with chloroquine and rifampin.

Infection with the new coronavirus has been declared an international health emergency. Its curative treatment is unknown and is the subject of several clinical trials. In addition, the concomitant association of COVID-19 with tuberculosis and the human immunodeficiency virus, hitherto never described, is potentially fatal. We report the illustrative case of a 32-year-old patient who presented this trifecta of infections and who did well under treatment with chloroquine and anti-mycobacterial drugs. This patient arrived at the ER with respiratory discomfort that had been evolving over a month with symptoms of flu and deterioration of her general condition. A chest CT scan revealed an aspect of lung miliary tuberculosis with isolation of Koch's bacilli in the sputum. A polymerization chain reaction (PCR) was positive for COVID-19 on a nasopharyngeal swab. HIV serology was positive. The course was marked by a spectacular clinical improvement and two negative COVID-19 PCR controls at the end of treatment (at days 9 and 10). Anti-tubercular drugs (especially, rifampin) are powerful enzyme inducers that can reduce the effectiveness of chloroquine in our patient. This therapeutic success may be linked to the effect of anti-tubercular drugs against SARS ncov-2, especially rifampin, inhibiting the formation of messenger RNAs of SARS ncov-2 or to the synergistic effect of chloroquine and rifampin. Researchers should explore the effect of these drugs on SARS ncov-2.

HCQ prophylaxis in COVID-19 did not show any QTc prolongation in Healthcare workers.

BACKGROUND: HCQ is a commonly recommended drug for the prophylaxis of COVID-19. One of its rare side-effect includes QTc prolongation. METHODS: This was a prospective, cross sectional and observational study conducted on Hydroxychloroquine (HCQ) among Healthcare Workers (HCWs) at Max Super Speciality Hospital, Saket, New Delhi, India. A 3-lead ECG (only limb leads, it does not require chest leads) was performed. The QTc cut offs were pre decided, QTC < 470 ms for males and <480 ms for females was considered within the normal limits and anything above this was regarded as QTc prolongation. RESULTS: There were 274 HCWs enrolled into the study, including 175 males and 99 females. Majority of the HCWs were young and had a mean age of 32.19 ± 9.29 years. Out of these, 218 were taking HCQ as per the Indian Council of Medical Research (ICMR) guidelines. The median cumulative dose being taken was 1600 mg and the median QTc of these participants was 390 ms in males and 391.5 ms in females. Subsequently, 33 participants were followed-up and found to have a median QTc of 389 ms and a cumulative dose of HCQ as 2000 mg. CONCLUSION: In conclusion, ours is a first study in the middle of the pandemic which showed that HCQ prophylaxis in young HCWs without comorbidities did not show any QTc prolongation.

Evidence-Based Risk Mitigation and Stratification During COVID-19 for Return to Interventional Pain Practice: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

BACKGROUND: Chronic pain patients require continuity of care even during the COVID-19 pandemic, which has drastically changed healthcare and other societal practices. The American Society of Interventional Pain Physicians (ASIPP) has created the COVID-ASIPP Risk Mitigation & Stratification (COVID-ARMS) Return to Practice Task Force in order to provide guidance for safe and strategic reopening. OBJECTIVES: The aims are to provide education and guidance for interventional pain specialists and their patients during the COVID-19 pandemic that minimizes COVID-related morbidity while allowing a return to interventional pain care. METHODS: The methodology utilized included the development of objectives and key questions with utilization of trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various regions, specialities, and groups. The literature pertaining to all aspects of COVID-19, specifically related to epidemiology, risk factors, complications, morbidity and mortality, and literature related to risk mitigation and stratification were reviewed. The principles of best evidence synthesis of available literature and grading for recommendations as described by the Agency for Healthcare Research and Quality (AHRQ) typically utilized in ASIPP guideline preparation was not utilized in these guidelines due to limitations because of their lack of available literature on COVID-19, risk mitigation and stratification. These guidelines are considered evidence -- informed with incorporation of best available research and practice knowledge. Consequently, these guidelines are considered evidence-informed with incorporation of best available research and practice knowledge. RESULTS: Numerous risk factors have emerged that predispose patients to contracting COVID-19 and/or having a more severe course of the infection. COVID-19 may have mild symptoms, even be asymptomatic, or may be severe and life threatening. Older age and certain comorbidities, such as underlying pulmonary or cardiovascular disease, have been associated with worse outcomes. In pain care, COVID-19 patients are a heterogeneous group with some individuals relatively healthy and having only a short course of manageable symptoms while others become critically ill. It is necessary to assess patients on a case-by-case basis and craft individualized care recommendations. A COVID-ARMS risk stratification tool was created to quickly and objectively assess patients. Interventional pain specialists and their patients may derive important benefits from evidence-informed risk stratification, protective strategies to prevent infection, and the gradual resumption of treatments and procedures to manage pain. LIMITATIONS: COVID-19 was an ongoing pandemic at the time during which these recommendations were developed. The pandemic has created a fluid situation in terms of evidence-informed guidance. As more and better evidence is gathered, these recommendations may be modified. CONCLUSIONS: Chronic pain patients require continuity of care but during the time of the COVID-19 pandemic, steps must be taken to stratify risks and protect patients from possible infection to safeguard them from COVID-19-related illness and transmitting the disease to others. Pain specialists should optimize telemedicine encounters with their pain patients, be cognizant of risks of COVID-19 morbidity, and take steps to evaluate risk-benefit on a case-by-case basis. Pain specialists may return to practice with lower-risk patients and appropriate safeguards.

Characteristics of scientific articles on COVID-19 published during the initial 3 months of the pandemic.

The COVID-19 pandemic has been characterized by an unprecedented amount of published scientific articles. The aim of this study is to assess the type of articles published during the first 3 months of the COVID-19 pandemic and to compare them with articles published during 2009 H1N1 swine influenza pandemic. Two operators independently extracted and assessed all articles on COVID-19 and on H1N1 swine influenza that had an abstract and were indexed in PubMed during the first 3 months of these pandemics. Of the 2482 articles retrieved on COVID-19, 1165 were included. Over half of them were secondary articles (590, 50.6%). Common primary articles were: human medical research (340, 59.1%), in silico studies (182, 31.7%) and in vitro studies (26, 4.5%). Of the human medical research, the vast majority were observational studies and cases series, followed by single case reports and one randomized controlled trial. Secondary articles were mainly reviews, viewpoints and editorials (373, 63.2%). Limitations were reported in 42 out of 1165 abstracts (3.6%), with 10 abstracts reporting actual methodological limitations. In a similar timeframe, there were 223 articles published on the H1N1 pandemic in 2009. During the COVID-19 pandemic there was a higher prevalence of reviews and guidance articles and a lower prevalence of in vitro and animal research studies compared with the H1N1 pandemic. In conclusions, compared to the H1N1 pandemic, the majority of early publications on COVID-19 does not provide new information, possibly diluting the original data published on this disease and consequently slowing down the development of a valid knowledge base on this disease. Also, only a negligible number of published articles reports limitations in the abstracts, hindering a rapid interpretation of their shortcomings. Researchers, peer reviewers, and editors should take action to flatten the curve of secondary articles.

Managing COVID-19 outbreak in Nigeria: matters arising.

Severe Acute Respiratory Syndrome - novel Coronavirus 2 (SARS-nCoV-2), was first reported in Wuhan, China, in December, 2019. Since the outbreak, the virus has infected more than 9,866,685 individuals, 4,983,029 treated and discharged and 495,692 deaths globally. The first Coronavirus Disease 2019 (COVID-19) in Nigeria was imported in February, 2020 and since then community transmission has been prevalent. As at the time of writing this report, Nigeria has reported about 23,298 cases of COVID-19, 8,253 treated and discharged and 554 deaths, giving a case mortality ratio of 2.4%. While responsible government agencies and international partners have been working hard to curtail the spread of the disease, we present in this report, some matters arising from managing COVID-19 pandemic in Nigeria; and proffered suggestions which could help not only in managing the current COVID-19 pandemic, but also for winning future outbreaks of public health significance with a view to curtailing global health security.

COVID-19 and NSAIDS: A Narrative Review of Knowns and Unknowns.

Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE) 2 receptors and increase susceptibility to the virus or worsen symptoms in existing disease. Adverse outcomes with COVID-19 have been linked to cytokine storm but the most effective way to address exaggerated inflammatory response is complex and unclear. The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19. NSAID use must also be categorized by whether the drugs are relatively low-dose over-the-counter oral products taken occasionally versus higher-dose or parenteral NSAIDs. Even if evidence emerged arguing for or against NSAIDs in this setting, it is unclear if this evidence would apply to all NSAIDs at all doses in all dosing regimens. Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses. There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis.

An Extensive Meta-Metagenomic Search Identifies SARS-CoV-2-Homologous Sequences in Pangolin Lung Viromes.

In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic data sets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic data set can be readily queried using web-based tools, meta-searches through all such data sets are less accessible. In this brief communication, we demonstrate such a meta-metagenomic approach, examining close matches to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all high-throughput sequencing data sets in the NCBI Sequence Read Archive accessible with the "virome" keyword. In addition to the homology to bat coronaviruses observed in descriptions of the SARS-CoV-2 sequence (F. Wu, S. Zhao, B. Yu, Y. M. Chen, et al., Nature 579:265-269, 2020, https://doi.org/10.1038/s41586-020-2008-3; P. Zhou, X. L. Yang, X. G. Wang, B. Hu, et al., Nature 579:270-273, 2020, https://doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in metavirome data sets generated from the lungs of deceased pangolins reported by Liu et al. (P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979). While analysis of these reads indicates the presence of a similar viral sequence in pangolin lung, the similarity is not sufficient to either confirm or rule out a role for pangolins as an intermediate host in the recent emergence of SARS-CoV-2. In addition to the implications for SARS-CoV-2 emergence, this study illustrates the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences.IMPORTANCE Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.