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1.
J Biomol Struct Dyn ; : 1-18, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2106892

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron is currently the most prevalent SARS-CoV-2 variant worldwide. Herein, we calculated molecular dynamics simulations of the trimeric spikeWT and SpikeBA.1 for 300 ns. Our results show that SpikeBA.1 has more conformational flexibility than SpikeWT. Our principal component analysis (PCA) allowed us to observe a broader spectrum of different conformations for SpikeBA.1, mainly at N-terminal domain (NTD) and receptor-binding domain (RBD). Such increased flexibility could contribute to decreased neutralizing antibody recognition of this variant. Our molecular dynamics data show that the RBDBA.1 easily visits an up-conformational state and the prevalent D614G mutation is pivotal to explain molecular dynamics results for this variant because to lost hydrogen bonding interactions between the residue pairs K854SC/D614SC, Y837MC/D614MC, K835SC/D614SC, T859SC/D614SC. In addition, SpikeBA.1 residues near the furin cleavage site are more flexible than in SpikeWT, probably due to P681H and D614G substitutions. Finally, dynamical cross-correlation matrix (DCCM) analysis reveals that D614G and P681H may allosterically affect the cleavage site S1/S2. Conversely, S2' site may be influenced by residues located between NTD and RBD of a neighboring protomer of the SpikeWT. Such communication may be lost in SpikeBA.1, explaining the changes of the cell tropism in the viral infection. In addition, the movements of the NTDWT and NTDBA.1 may modulate the RBD conformation through allosteric effects. Taken together, our results explain how the structural aspects may explain the observed gains in infectivity, immune system evasion and transmissibility of the Omicron variant.Communicated by Ramaswamy H. Sarma.

2.
Comput Biol Med ; 151(Pt A): 106262, 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2095220

ABSTRACT

Due to its high transmissibility, Omicron BA.1 ousted the Delta variant to become a dominating variant in late 2021 and was replaced by more transmissible Omicron BA.2 in March 2022. An important question is which new variants will dominate in the future. Topology-based deep learning models have had tremendous success in forecasting emerging variants in the past. However, topology is insensitive to homotopic shape evolution in virus-human protein-protein binding, which is crucial to viral evolution and transmission. This challenge is tackled with persistent Laplacian, which is able to capture both the topological change and homotopic shape evolution of data. Persistent Laplacian-based deep learning models are developed to systematically evaluate variant infectivity. Our comparative analysis of Alpha, Beta, Gamma, Delta, Lambda, Mu, and Omicron BA.1, BA.1.1, BA.2, BA.2.11, BA.2.12.1, BA.3, BA.4, and BA.5 unveils that Omicron BA.2.11, BA.2.12.1, BA.3, BA.4, and BA.5 are more contagious than BA.2. In particular, BA.4 and BA.5 are about 36% more infectious than BA.2 and are projected to become new dominant variants by natural selection. Moreover, the proposed models outperform the state-of-the-art methods on three major benchmark datasets for mutation-induced protein-protein binding free energy changes. Our key projection about BA4 and BA.5's dominance made on May 1, 2022 (see arXiv:2205.00532) became a reality in late June 2022.

3.
Comput Struct Biotechnol J ; 20: 5870-5872, 2022.
Article in English | MEDLINE | ID: covidwho-2086109

ABSTRACT

Our hypothesis about evolution of the COVID-19 pandemic foresees an inverse relation between infectivity (R0) and lethality (L) of SARS-CoV-2. The above parameters are driven by a continuing mutation process granting the virus a clear survival advantage over virulence. For interpreting this relation we adopted a simple equation, R0 × L ≈ k, by which R0 and L depend upon a constant k, that corresponds to an intrinsic property of the viral species involved. The hypothesis was verified by following changes of the R0 and L terms of the formula in the different variants of SARS-CoV-2 that progressively appeared. A further validation came when the equation was applied to pandemic and epidemic influenza type A viruses, Ebola virus and measles virus. We believe this equation that considers virus biology in Darwinian terms could be extremely useful to better face infectious viral threats and validate virus-host molecular interactions relevant to viral pathogenesis.

4.
BioTech (Basel) ; 11(4)2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-2071231

ABSTRACT

Omicron BA.2.75 may become the next globally dominant strain of COVID-19 in 2022. The BA.2.75 sub-variant has acquired more mutations (9) in spike protein and other genes of SARS-CoV-2 than any other variant. Thus, its chemical composition and thermodynamic properties have changed compared with earlier variants. In this paper, the Gibbs energy of the binding and antigen-receptor binding rate was reported for the BA.2.75 variant. Gibbs energy of the binding of the Omicron BA.2.75 variant is more negative than that of the competing variants BA.2 and BA.5.

5.
Meteorological Applications ; 29(5), 2022.
Article in English | Web of Science | ID: covidwho-2068579

ABSTRACT

Laboratory experiments have revealed the meteorological sensitivity of the coronavirus disease 2019 (COVID-19) virus. However, no consensus has been reached about how outdoor meteorological conditions modulate the virus transmission as it is also constrained by non-meteorological conditions. Here, we identify the outbreak's evolution stage, constrained least by non-meteorological conditions, by searching the maximum correlation coefficient between the ultraviolet flux and the growth rate of cumulative confirmed cases at the country level. At this least-constrained stage, the cumulative cases count around 1300-3200, and the count's daily growth rate correlates with the ultraviolet flux and temperature significantly (correlation coefficients r = -0.54 +/- 0.09 and -0.39 +/- 0.10 at p<0.01$$ p, respectively), but not with precipitation, humidity, and wind. The ultraviolet correlation exhibits a delay of about 7 days, providing a meteorological measure of the incubation period. Our work reveals a seasonality of COVID-19 and a high risk of a pandemic resurgence in winter, implying a need for seasonal adaption in public policies.

6.
Zoonoses ; 1(13), 2021.
Article in English | CAB Abstracts | ID: covidwho-2025746

ABSTRACT

As the novel coronavirus SARS-CoV-2 spread around the world, multiple waves of variants emerged, thus leading to local or global population shifts during the pandemic. A new variant named Omicron (PANGO lineage B.1.1.529), which was first discovered in southern Africa, has recently been proposed by the World Health Organization to be a Variant of Concern. This variant carries an unusually large number of mutations, particularly on the spike protein and receptor binding domain, in contrast to other known major variants. Some mutation sites are associated with enhanced viral transmission, infectivity, and pathogenicity, thus enabling the virus to evade the immune protective barrier. Given that the emergence of the Omicron variant was accompanied by a sharp increase in infection cases in South Africa, the variant has the potential to trigger a new global epidemic peak. Therefore, continual attention and a rapid response are required to decrease the possible risks to public health.

7.
Acta Veterinaria et Zootechnica Sinica ; 53(6):2024-2028, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-2025545

ABSTRACT

This study aimed to analyze the proliferation characteristics of porcine deltacoronavirus (PDCoV) in suspension cultured porcine kidney cells LLC-PK1, so as to provide Candidate cell for large-scale production of PDCoV inactivated vaccine. LLC-PK1 cells were suspended by gradually decreasing serum method. PDCoV adaptive monoclonal cell lines were screened by limited dilution method. Indirect immunofluorescence method was used to identify the infectivity of PDCoV. The initial cell density, MOI, time of receiving virus collection and TPCK pancreatin concentration were screened to determine the best suspension culture conditions. The suspension cell strain LLC-PK1Sa which can proliferate PDCoV efficiently was screened out;PDCoV can specifically infect LLC-PK1 cells;PDCoV inoculated LLC-PK1Sa cells with a density of 2 x 106 cells.mL-1 according to the MOI of 10-3, When the final concentration of TPCK pancreatin reached 7.5 g.mL-1, the titer of virus solution harvested 48 h after inoculation was the highest. In this study, the efficient proliferation of PDCoV in LLC-PK1Sa suspension cells was realized for the first time, and the suspension culture conditions were preliminarily optimized, which could provide theoretical reference for large-scale production of PDCoV inactivated vaccine.

8.
Pharmazeutische Zeitung ; 167(8):46-47, 2022.
Article in German | EMBASE | ID: covidwho-2006805
9.
Indoor Air ; 32(8): e13083, 2022 08.
Article in English | MEDLINE | ID: covidwho-2005268

ABSTRACT

This systematic review aims to present an overview of the current aerosol sampling methods (and equipment) being used to investigate the presence of SARS-CoV-2 in the air, along with the main parameters reported in the studies that are essential to analyze the advantages and disadvantages of each method and perspectives for future research regarding this mode of transmission. A systematic literature review was performed on PubMed/MEDLINE, Web of Science, and Scopus to assess the current air sampling methodologies being applied to SARS-CoV-2. Most of the studies took place in indoor environments and healthcare settings and included air and environmental sampling. The collection mechanisms used were impinger, cyclone, impactor, filters, water-based condensation, and passive sampling. Most of the reviewed studies used RT-PCR to test the presence of SARS-CoV-2 RNA in the collected samples. SARS-CoV-2 RNA was detected with all collection mechanisms. From the studies detecting the presence of SARS-CoV-2 RNA, fourteen assessed infectivity. Five studies detected viable viruses using impactor, water-based condensation, and cyclone collection mechanisms. There is a need for a standardized protocol for sampling SARS-CoV-2 in air, which should also account for other influencing parameters, including air exchange ratio in the room sampled, relative humidity, temperature, and lighting conditions.


Subject(s)
Air Pollution, Indoor , COVID-19 , Humans , RNA, Viral , Respiratory Aerosols and Droplets , SARS-CoV-2 , Water
10.
Forensic Sci Med Pathol ; 2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-2000104

ABSTRACT

The persistence and infectivity of SARS-CoV-2 in different postmortem COVID-19 specimens remain unclear despite numerous published studies. This information is essential to improve corpses management related to clinical biosafety and viral transmission in medical staff and the public community. We aim to understand SARS-CoV-2 persistence and infectivity in COVID-19 corpses. We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocols. A systematic literature search was performed in PubMed, Science Direct Scopus, and Google Scholar databases using specific keywords. We critically reviewed the collected studies and selected the articles that met the criteria. We included 33 scientific papers that involved 491 COVID-19 corpses. The persistence rate and maximum postmortem interval (PMI) range of the SARS-CoV-2 findings were reported in the lungs (138/155, 89.0%; 4 months), followed by the vitreous humor (7/37, 18.9%; 3 months), nasopharynx/oropharynx (156/248, 62.9%; 41 days), abdominal organs (67/110, 60.9%; 17 days), skin (14/24, 58.3%; 17 days), brain (14/31, 45.2%; 17 days), bone marrow (2/2, 100%; 12 days), heart (31/69, 44.9%; 6 days), muscle tissues (9/83, 10.8%; 6 days), trachea (9/20, 45.0%; 5 days), and perioral tissues (21/24, 87.5%; 3.5 days). SARS-CoV-2 infectivity rates in viral culture studies were detected in the lungs (9/15, 60%), trachea (2/4, 50%), oropharynx (1/4, 25%), and perioral (1/4, 25%) at a maximum PMI range of 17 days. The SARS-CoV-2 persists in the human body months after death and should be infectious for weeks. This data should be helpful for postmortem COVID-19 management and viral transmission preventive strategy.

11.
The North American Journal of Economics and Finance ; 63:101787, 2022.
Article in English | ScienceDirect | ID: covidwho-1996451

ABSTRACT

Motivated by the stochastic SIS model, this paper aims to incorporate the stochastic transmission shock (e.g., COVID−19) into the standard portfolio theory, and explores the optimal rules with respect to infections. The impact of COVID−19 is decomposed into two dimensions such as infectivity (denoted by R0) and infection rate (measured by I). The results indicate that infectivity mainly affects consumption, whereas the investment rule is merely governed by infection rate. Moreover, we find that higher infections lead to less sensitivity and smoother consumption compared with normal times. However, the sensitivity and volatility of investment with respect to infections present a U-shape and hump-shape, respectively. Notably, we shed new lights on the effect of transmission uncertainty and risk-aversion with pandemic shock. The innovative attempt of this paper not only enriches the research of epidemiology in the field of economics, but also provides a paradigm for studying investor’s behavior under the normalization of epidemic situations.

12.
Folia Microbiol (Praha) ; 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1990781

ABSTRACT

The Delta variant is one of the alarming variants of the SARS-CoV-2 virus that have been immensely detrimental and a significant cause of the prolonged pandemic (B.1.617.2). During the SARS-CoV-2 pandemic from December 2020 to October 2021, the Delta variant showed global dominance, and afterwards, the Omicron variant showed global dominance. Delta shows high infectivity rate which accounted for nearly 70% of the cases after December 2020. This review discusses the additional attributes that make the Delta variant so infectious and transmissible. The study also focuses on the significant mutations, namely the L452R and T478K present on the receptor-binding domain of spike (S)-glycoprotein, which confers specific alterations to the Delta variant. Considerably, we have also highlighted other notable factors such as the immune escape, infectivity and re-infectivity, vaccine escape, Ro number, S-glycoprotein stability, cleavage pattern, and its binding affinity with the host cell receptor protein. We have also emphasized clinical manifestations, symptomatology, morbidity, and mortality for the Delta variant compared with other significant SARS-CoV-2 variants. This review will help the researchers to get an elucidative view of the Delta variant to adopt some practical strategies to minimize the escalating spread of the SARS-CoV-2 Delta variant.

13.
Viruses ; 14(8)2022 08 15.
Article in English | MEDLINE | ID: covidwho-1987995

ABSTRACT

OBJECTIVE: There is extensive evidence that SARS-CoV-2 replicates in the gastrointestinal tract. However, the infectivity of virions in feces is poorly documented. Although the primary mode of transmission is airborne, the risk of transmission from contaminated feces remains to be assessed. DESIGN: The persistence of SARS-CoV-2 (infectivity and RNA) in human and animal feces was evaluated by virus isolation on cell culture and RT-qPCR, respectively. The exposure of golden Syrian hamsters to experimentally contaminated feces through intranasal inoculation has also been tested to assess the fecal-oral transmission route. RESULTS: For periods that are compatible with average intestinal transit, the SARS-CoV-2 genome was noticeably stable in human and animal feces, contrary to the virus infectivity that was reduced in a time- and temperature-dependent manner. In human stools, this reduction was variable depending on the donors. Viral RNA was excreted in the feces of infected hamsters, but exposure of naïve hamsters to feces of infected animals did not lead to any productive infection. Conversely, hamsters could be experimentally infected following exposure to spiked fresh feces. CONCLUSION: Infection following exposure to naturally contaminated feces has been suspected but has not been established so far. The present work demonstrates that SARS-CoV-2 rapidly lost infectivity in spiked or naturally infected feces. Although the possibility of persistent viral particles in human or animal feces cannot be fully ruled out, SARS-CoV-2 transmission after exposure to contaminated feces is unlikely.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Feces , Humans , Mesocricetus , RNA, Viral
14.
Int J Infect Dis ; 122: 733-740, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1983198

ABSTRACT

OBJECTIVES: Ivermectin, an antiparasitic agent, also has antiviral properties. In this study, we aimed to assess whether ivermectin has anti-SARS-CoV-2 activity. METHODS: In this double-blinded trial, we compared patients receiving ivermectin for 3 days versus placebo in nonhospitalized adult patients with COVID-19. A reverse transcriptase-polymerase chain reaction from a nasopharyngeal swab was obtained at recruitment and every 2 days for at least 6 days. The primary endpoint was a reduction of viral load on the sixth day as reflected by cycle threshold level >30 (noninfectious level). The primary outcome was supported by the determination of viral-culture viability. RESULTS: Of 867 patients screened, 89 were ultimately evaluated per-protocol (47 ivermectin and 42 placeboes). On day 6, the odds ratio (OR) was 2.62 (95% confidence interval [CI]: 1.09-6.31) in the ivermectin arm, reaching the endpoint. In a multivariable logistic regression model, the odds of a negative test on day 6 were 2.28 times higher in the ivermectin group but reached significance only on day 8 (OR 3.70; 95% CI: 1.19-11.49, P = 0.02). Culture viability on days 2 to 6 was positive in 13.0% (3/23) of ivermectin samples versus 48.2% (14/29) in the placebo group (P = 0.008). CONCLUSION: There were lower viral loads and less viable cultures in the ivermectin group, which shows its anti-SARS-CoV-2 activity. It could reduce transmission in these patients and encourage further studies with this drug.


Subject(s)
COVID-19 , Adult , COVID-19/drug therapy , Double-Blind Method , Humans , Ivermectin/pharmacology , Ivermectin/therapeutic use , SARS-CoV-2 , Treatment Outcome , Viral Load
15.
Siam Journal on Applied Mathematics ; 82(3):899-923, 2022.
Article in English | Web of Science | ID: covidwho-1978565

ABSTRACT

Asymptomatic infection and transmission are common for quite a few directly or indirectly transmitted diseases such as COVID-19, cholera, and Zika fever. In this paper, we propose a susceptible-infective-asymptomatic-recovered patch model to address the influence of asymptomatic infections on the spatial spread of infectious diseases. The multipatch basic reproduction number 72.0 of the model is defined and shown to be a threshold quantity for disease eradication and persistence. Namely, the disease disappears if 72.0 < 1 whereas it spreads otherwise. The monotonicity of 72.0 with respect to the dispersal rates of the symptomatic and asymptomatic populations is investigated. In particular, for the two-patch case, 72.0 is either strictly decreasing or strictly increasing or constant in terms of dispersal rates. However, nonmonotonic dependence can occur with movement between three or more patches. The asymptotic profiles of the endemic equilibrium (when it exists) as one or all dispersal rates approach zero or infinity are studied. Interestingly, an increase in infectious dispersal may decrease 72.0 but increase the number of nonsusceptible individuals. Analytical and numerical results confirm that ignoring asymptomatic carriers not only significantly underestimates the infection risk but also impairs the efficacy of travel restrictions.

16.
J Dent Res ; 101(12): 1421-1423, 2022 11.
Article in English | MEDLINE | ID: covidwho-1962582
17.
Clin Microbiol Infect ; 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1936217

ABSTRACT

OBJECTIVE: To define the relationship of SARS-CoV-2 antigen, viral load determined by RT-qPCR, and viral culture detection. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals and thereby inform how and where to most appropriately deploy antigen and nucleic acid amplification-based diagnostic testing modalities. METHODS: We compared the antigen testing results from three lateral flow and one microfluidics assay to viral culture detection and viral load determination performed in parallel in up to 189 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. RESULTS: Antigen tests were predictive of viral culture positivity, with the LumiraDx microfluidics method showing enhanced sensitivity (90%; 95% CI 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver operator characteristic curves of 0.94 to 0.97 and 0.92, respectively. A viral load threshold of 100 000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Adjusting for sample dilution inherent in our study design, sensitivities of antigen tests were ≥95% for detection of viral culture positive samples with viral loads >106 genome copies/mL, although specificity of antigen testing was imperfect. DISCUSSION: Antigen testing results and viral culture were correlated. For culture positive samples, the sensitivity of antigen tests was high at high viral loads that are likely associated with significant infectivity. Therefore, our data provides support for use of antigen testing in ruling out infectivity at the time of sampling.

18.
Viruses ; 14(7)2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1939025

ABSTRACT

From the beginning of the COVID-19 pandemic, researchers assessed the impact of the disease in terms of loss of life, medical load, economic damage, and other key metrics of resiliency and consequence mitigation; these studies sought to parametrize the critical components of a disease transmission model and the resulting analyses were informative but often lacked critical parameters or a discussion of parameter sensitivities. Using SARS-CoV-2 as a case study, we present a robust modeling framework that considers disease transmissibility from the source through transport and dispersion and infectivity. The framework is designed to work across a range of particle sizes and estimate the generation rate, environmental fate, deposited dose, and infection, allowing for end-to-end analysis that can be transitioned to individual and population health models. In this paper, we perform sensitivity analysis on the model framework to demonstrate how it can be used to advance and prioritize research efforts by highlighting critical parameters for further analyses.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics
19.
BMJ : British Medical Journal (Online) ; 378, 2022.
Article in English | ProQuest Central | ID: covidwho-1932683

ABSTRACT

While offering secondary care at home may suit some, and could reduce costs, it is clear that virtual wards need adequate staffing, and careful planning and evaluation, and cannot fully replace traditional hospital wards. A summary of research from NIHR tracks the uptake of mastectomy and bilateral salpingo-oophorectomy among healthy women who carry BRCA1 or BRCA2 genes and are at high risk of cancer (doi:10.1136/bmj.o258).3 Although most women opted to proceed with surgery, others did not, suggesting that more work is needed to understand their reasons and to examine alternative strategies. Claire Johnston and colleagues use available evidence on infectivity and covid-19 to help doctors share pragmatic and straightforward advice with patients and the public (doi:10.1136/bmj-2020-061402).4 Their work comes at a time when covid is re-exerting its pressure on health systems, with rising case numbers having an impact on hospital beds and staffing levels (doi:10.1136/bmj.o1638).5 In such a climate, complaints about clinical care, delays, overcrowding, staffing, and supply problems are likely to rise.

20.
Front Cell Infect Microbiol ; 12: 885482, 2022.
Article in English | MEDLINE | ID: covidwho-1917202

ABSTRACT

[This corrects the article DOI: 10.3389/fcimb.2021.777212.].

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