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1.
Med Rev (Berl) ; 2(1): 3-22, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1879342

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has caused immense losses in human lives and the global economy and posed significant challenges for global public health. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has evolved, thousands of single nucleotide variants (SNVs) have been identified across the viral genome. The roles of individual SNVs in the zoonotic origin, evolution, and transmission of SARS-CoV-2 have become the focus of many studies. This review summarizes recent comparative genomic analyses of SARS-CoV-2 and related coronaviruses (SC2r-CoVs) found in non-human animals, including delineation of SARS-CoV-2 lineages based on characteristic SNVs. We also discuss the current understanding of receptor-binding domain (RBD) evolution and characteristic mutations in variants of concern (VOCs) of SARS-CoV-2, as well as possible co-evolution between RBD and its receptor, angiotensin-converting enzyme 2 (ACE2). We propose that the interplay between SARS-CoV-2 and host RNA editing mechanisms might have partially resulted in the bias in nucleotide changes during SARS-CoV-2 evolution. Finally, we outline some current challenges, including difficulty in deciphering the complicated relationship between viral pathogenicity and infectivity of different variants, and monitoring transmission of SARS-CoV-2 between humans and animals as the pandemic progresses.

2.
Chemical Engineering Journal ; : 137067, 2022.
Article in English | ScienceDirect | ID: covidwho-1850791

ABSTRACT

Chloroxylenol (PCMX) is widely used as disinfectant since the epidemic outbreak due to its effective killing of Covid-19 virus. Its stable chemical properties make it frequently detected in surface water. Herein, we successfully modified Fe3O4 nanoparticles with S-WO3 (X-Fe3O4/S-WO3) to accelerate the Fe2+/Fe3+ cycle. The composite has outstanding PCMX degradation and peroxymonosulfate (PMS) decomposition efficiency over a wide pH range (3.0∼9.0). 80-Fe3O4/S-WO3/PMS system not only increased PMS decomposition efficiency from 27.7% to 100.0%, but also realized an enhancement of PCMX degradation efficiency by 16 times in comparison with that of Fe3O4 alone. The catalyst utilization efficiency reached 0.3506 mmol∙g-1∙min-1 which stands out among most Fenton-like catalysts. The composite has excellent degradation ability to a variety of emerging pollutants, such as antibiotics, drugs, phenols and endocrine disrupters, and at least a 90% removal efficiency reached in 10 min. The degradation of PCMX was dominated by HO•, SO4•- and 1O2. The degradation pathways of PCMX were analyzed in detail. The component WS2 in S-WO3 plays a co-catalytic role instead of WO3. And the exposed active W4+surf. efficiently enhanced the Fe3+/Fe2+ cycle, thereby complete PMS decomposition and high catalytic efficiency were achieved. Our findings clarify that applying two-dimensional transition metal sulfide WS2 to modify heterogeneous Fe3O4 is a feasible strategy to improve Fenton-like reaction and provide a promising catalyst for PCMX degradation.

4.
Mol Biol Evol ; 39(3)2022 03 02.
Article in English | MEDLINE | ID: covidwho-1722547

ABSTRACT

In new epidemics after the host shift, the pathogens may experience accelerated evolution driven by novel selective pressures. When the accelerated evolution enters a positive feedback loop with the expanding epidemics, the pathogen's runaway evolution may be triggered. To test this possibility in coronavirus disease 2019 (COVID-19), we analyze the extensive databases and identify five major waves of strains, one replacing the previous one in 2020-2021. The mutations differ entirely between waves and the number of mutations continues to increase, from 3-4 to 21-31. The latest wave in the fall of 2021 is the Delta strain which accrues 31 new mutations to become highly prevalent. Interestingly, these new mutations in Delta strain emerge in multiple stages with each stage driven by 6-12 coding mutations that form a fitness group. In short, the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the oldest to the youngest wave, and from the earlier to the later stages of the Delta wave, is a process of acceleration with more and more mutations. The global increase in the viral population size (M(t), at time t) and the mutation accumulation (R(t)) may have indeed triggered the runaway evolution in late 2020, leading to the highly evolved Alpha and then Delta strain. To suppress the pandemic, it is crucial to break the positive feedback loop between M(t) and R(t), neither of which has yet to be effectively dampened by late 2021. New waves after Delta, hence, should not be surprising.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/genetics , Humans , Mutation , Pandemics , SARS-CoV-2/genetics
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325393

ABSTRACT

Objectives: To discuss the prevention and containment of COVID-19 at a general hospital in Shenzhen China;to analyze the epidemiological and clinical characteristics of its confirmed patients, which is intended to provide a model for other hospitals in COVID-19 management. Methods: : The General Hospital of Shenzhen University sets up 4 medical zones relative to the COVID-19 prevention and containment. In so doing, the suspected patients classified into different kind of ward receive different treatment (Classified and Separated Treatment). The epidemiological distribution and clinical characteristics of 28 confirmed cases in the hospital were analyzed. Results: : There are no medical personnel infected cases, no cross-infection among the patients in the hospital, and no misdiagnosis or missed diagnosis of COVID-19. The majority of cases in the group is from 15 to 60 years old, 25 cases had a definite travel history or close contact history in the epidemic area, and parents and spouses of the confirmed patients are the main contact groups. Fever and respiratory symptoms have a high proportion, 4 diarrhea and 4 asymptomatic cases. Additionally, the decrease of lymphocyte is observed in 8 cases. Chest CT scan shows viral pneumonia in 14 cases,All patients were confirmed by nucleic acid tests. Conclusions: : Classified and Separated Treatment facilitates management of COVID-19 in the general hospital. Relative to suspected patients in the general hospital, diagnosis matters more than treatment. Epidemiological history, lymphocyte count, and chest CT scan play an important role as the indicator in early diagnosis of COVID-19.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325284

ABSTRACT

Background: The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and discharge assessment for COVID-19. Methods: The baseline included 285 adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Guangzhou Eighth People's Hospital. We started the Observation on Jan 20, 2020, and acquired all their definite clinical outcome (becoming RP or keeping normal during post-discharge surveillance) by Mar 10, 2020. The dynamic clinical data of patients during observation were prospectively collected and analyzed. Univariate and multivariate-adjusted logistic regression were used to explore the risk factors related to RP events in COVID-19 patients. Results: By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0-8·0). Age, sex, epidemiological history, clinical symptoms and underlying diseases were similar between RP and non-RP patients (p>0.05). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p<0.05). Elder RP patients (≥ 60 years old) were more likely to be symptomatic compared to younger patients (7/8, 87.5% vs. 3/19, 18.8%, p=0.001) at readmission. A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50-13.57 for N gene;aOR: 9.64, 95% CI: 3.91-23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69;95% CI: 0.50-0.95) were associated with RP events. Conclusions: RP events occurred in nearly 10% of COVID-19 patients which deserves globally attention. During hospitalization, patients’ low efficiency of viral clearance was a risk factor for RP event. Elderly RP patients were more likely to develop clinical symptoms. To reduce the possibility of reinfection and readmission during the management of COVID-19, more rigorously monitoring on patients’ viral load should be carried out especially in elder patients and later stage of hospitalization.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324340

ABSTRACT

Background: Shenzhen implement classification management to prevent and control coronavirus disease 2019 (COVID-19) outbreak. Individuals with epidemic histories (came from Hubei and any other affected regions), but without symptoms were instructed to take home quarantine for 14 days and nucleic acid testing (NAT) for SARS-CoV-2. We described the infection status of the home-quarantined individuals, and effects of community control strategies in the three incubations after Wuhan closure in Shenzhen. Methods: : This was a descriptive research, the sample size was 2,004 individuals based on multistage sampling during the pre-investigation. And the formal investigation expanded the sample size to 57,012 individuals based on pre-investigation. A single throat swab was collected from each individual for nucleic acid testing (NAT) by reverse transcription-polymerase chain reaction (RT-PCR). NAT was performed by a third-party institution. We collected information related to demographics, disease history, travel history, and personal protective measures before home quarantine, and monitored close-contact histories using the We Chat questionnaire. Results: : The total infection rate of home-quarantined individuals was 0.12‰ (95% CI: 0.05‰–0.24‰) out of the total sample size of 59,016. The detection period for seven confirmed cases was primarily concentrated between February 8 and 18, 2020, which was during the second incubation period after Wuhan's closure. The home quarantined individuals with epidemic histories (came from Hubei and any other affected regions) were considered the high risk population during the first two incubations after Wuhan’s closure. No positive cases were detected from February 25 to March 5(the third incubation after Wuhan’s closure). The number of newly-confirmed cases per day was 0 for eight consecutive days from February 22 to 29 in Shenzhen. Conclusions: : The community control strategies for home-quarantined individuals with epidemic histories (came from Hubei and any other affected regions), but without symptoms to take the NAT in the first two incubations is effective to control COVID-19. But it is not advocating for home-quarantined person to take the NAT since the third incubation.

8.
Ann Neurol ; 91(4): 568-574, 2022 04.
Article in English | MEDLINE | ID: covidwho-1680263

ABSTRACT

Coronavirus disease 2019 (COVID-19) severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2 infection) can lead to intensive care unit (ICU) admission and critical illness myopathy (CIM). We examined 3 ICU patients with COVID-19 who required mechanical ventilation for pneumonia and developed CIM. Pathological examination of the skeletal muscle biopsies revealed myopathic changes consistent with CIM, variable inflammation with autophagic vacuoles, SARS-CoV immunostaining + fibers/granules, and electron microscopy findings of mitochondrial abnormalities and coronavirus-like particles. Although mitochondrial dysfunction with compromised energy production is a critical pathogenic mechanism of non-COVID-19-associated CIM, in our series of COVID-19-associated CIM, myopathic changes including prominent mitochondrial damage suggest a similar mechanism and association with direct SARS-CoV-2 muscle infection. ANN NEUROL 2022;91:568-574.


Subject(s)
COVID-19/complications , COVID-19/virology , Critical Illness , Muscular Diseases/etiology , Muscular Diseases/virology , SARS-CoV-2 , Adult , Aged , Autophagy , Fatal Outcome , Female , Humans , Inflammation/pathology , Intensive Care Units , Male , Middle Aged , Mitochondria/pathology , Muscle, Skeletal/pathology , Vacuoles/pathology
9.
Int J Environ Res Public Health ; 19(3)2022 01 27.
Article in English | MEDLINE | ID: covidwho-1674612

ABSTRACT

The Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2) was an outbreak in December, 2019 and rapidly spread to the world. All variants of SARS-CoV-2, including the globally and currently dominant Delta variant (Delta-SARS-CoV-2), caused severe disease and mortality. Among all variants, Delta-SARS-CoV-2 had the highest transmissibility, growth rate, and secondary attack rate than other variants except for the new variant of Omicron that still exists with many unknown effects. In Taiwan, the pandemic Delta-SARS-CoV-2 began in Pingtung from 14 June 2021 and ceased at 11 July 2021. Seventeen patients were infected by Delta-SARS-CoV-2 and 1 person died during the Pingtung outbreak. The Public Health Bureau of Pingtung County Government stopped the Delta-SARS-CoV-2 outbreak within 1 month through measures such as epidemic investigation, rapid gene sequencing, rapidly expanding isolation, expanded screening of the Delta-SARS-CoV-2 antigen for people who lived in regional villages, and indirect intervention, including rapid vaccination, short lockdown period, and travel restrictions. Indirect environmental factors, such as low levels of air pollution, tropic weather in the summer season, and rural areas might have accelerated the ability to control the Delta-SARS-CoV-2 spread. This successful experience might be recommended as a successful formula for the unvaccinated or insufficiently vaccinated regions.


Subject(s)
COVID-19 , Communicable Disease Control , Disease Outbreaks , Humans , SARS-CoV-2 , Taiwan/epidemiology
11.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295864

ABSTRACT

The standard practice of presenting one viral sequence for each infected individual implicitly assumes low within-host genetic diversity. It places the emphasis on the viral evolution between, rather than within, hosts. To determine this diversity, we collect SARS-CoV-2 samples from the same patient multiple times. Our own data in conjunction with previous reports show that two viral samples collected from the same individual are often very different due to the substantial within-host diversity. Each sample captures only a small part of the total diversity that is transiently and locally released from infected cells. Hence, the global SARS-CoV-2 population is a meta-population consisting of the viruses in all the infected hosts, each of which harboring a genetically diverse sub-population. Advantageous mutations must be present first as the within-host diversity before they are revealed as between-host polymorphism. The early detection of such diversity in multiple hosts could be an alarm for potentially dangerous mutations. In conclusion, the main forces of viral evolution, i.e., mutation, drift, recombination and selection, all operate within hosts and should be studied accordingly. Several significant implications are discussed.

12.
Zool Res ; 42(6): 834-844, 2021 11 18.
Article in English | MEDLINE | ID: covidwho-1515719

ABSTRACT

Understanding the zoonotic origin and evolution history of SARS-CoV-2 will provide critical insights for alerting and preventing future outbreaks. A significant gap remains for the possible role of pangolins as a reservoir of SARS-CoV-2 related coronaviruses (SC2r-CoVs). Here, we screened SC2r-CoVs in 172 samples from 163 pangolin individuals of four species, and detected positive signals in muscles of four Manis javanica and, for the first time, one M. pentadactyla. Phylogeographic analysis of pangolin mitochondrial DNA traced their origins from Southeast Asia. Using in-solution hybridization capture sequencing, we assembled a partial pangolin SC2r-CoV (pangolin-CoV) genome sequence of 22 895 bp (MP20) from the M. pentadactyla sample. Phylogenetic analyses revealed MP20 was very closely related to pangolin-CoVs that were identified in M. javanica seized by Guangxi Customs. A genetic contribution of bat coronavirus to pangolin-CoVs via recombination was indicated. Our analysis revealed that the genetic diversity of pangolin-CoVs is substantially higher than previously anticipated. Given the potential infectivity of pangolin-CoVs, the high genetic diversity of pangolin-CoVs alerts the ecological risk of zoonotic evolution and transmission of pathogenic SC2r-CoVs.


Subject(s)
COVID-19/veterinary , Evolution, Molecular , Pangolins/virology , SARS-CoV-2/genetics , Animals , Genome, Viral , Phylogeny , RNA, Viral/genetics
13.
China CDC Wkly ; 3(41): 869-877, 2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1498479

ABSTRACT

INTRODUCTION: Assessing the effects of non-pharmaceutical interventions (NPIs) and vaccines on controlling the coronavirus disease 2019 (COVID-19) is key for each government to optimize the anti-contagion policy according to their situation. METHODS: We proposed the Braking Force Model on Virus Transmission to evaluate the validity and efficiency of NPIs and vaccines. This model classified the NPIs and the administration of vaccines at different effectiveness levels and forecasted the duration required to control the pandemic, providing an indication of the future trends of the pandemic wave. RESULTS: This model was applied to study the effectiveness of the most commonly used NPIs according to the historic pandemic waves in different countries and regions. It was found that when facing an outbreak, only strict lockdown would give efficient control of the pandemic; the other NPIs were insufficient to promptly and effectively reduce virus transmission. Meanwhile, our results showed that NPIs would likely only slow down the pandemic's progression and maintain a low transmission level but fail to eradicate the disease. Only vaccination would likely have had a better chance of success in ending the pandemic. DISCUSSION: Based on the Braking Force Model, a pandemic control strategy framework has been devised for policymakers to determine the commencement and duration of appropriate interventions, with the aim of obtaining a balance between public health risk management and economic recovery.

15.
Nucleic Acids Res ; 50(D1): D888-D897, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1462429

ABSTRACT

The genomic variations of SARS-CoV-2 continue to emerge and spread worldwide. Some mutant strains show increased transmissibility and virulence, which may cause reduced protection provided by vaccines. Thus, it is necessary to continuously monitor and analyze the genomic variations of SARS-COV-2 genomes. We established an evaluation and prewarning system, SARS-CoV-2 variations evaluation and prewarning system (VarEPS), including known and virtual mutations of SARS-CoV-2 genomes to achieve rapid evaluation of the risks posed by mutant strains. From the perspective of genomics and structural biology, the database comprehensively analyzes the effects of known variations and virtual variations on physicochemical properties, translation efficiency, secondary structure, and binding capacity of ACE2 and neutralizing antibodies. An AI-based algorithm was used to verify the effectiveness of these genomics and structural biology characteristic quantities for risk prediction. This classifier could be further used to group viral strains by their transmissibility and affinity to neutralizing antibodies. This unique resource makes it possible to quickly evaluate the variation risks of key sites, and guide the research and development of vaccines and drugs. The database is freely accessible at www.nmdc.cn/ncovn.


Subject(s)
COVID-19/virology , Databases, Factual , Mutation , SARS-CoV-2/genetics , Algorithms , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Neutralizing/metabolism , Artificial Intelligence , DNA Primers , Genome, Viral , Humans
16.
Signal Transduct Target Ther ; 6(1): 342, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415923

ABSTRACT

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.


Subject(s)
COVID-19 , Carrier State/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Transcriptome/immunology , Adolescent , Adult , COVID-19/genetics , COVID-19/immunology , Female , Humans , Male , Middle Aged , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/genetics
18.
Science ; 373(6557): 918-922, 2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367378

ABSTRACT

Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare, heterozygous single-nucleotide variants in the MX1 gene. MX1 codes for myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase known to control IAV infections in transgenic mice. Most of the MxA variants identified lost the ability to inhibit avian IAVs, including H7N9, in transfected human cell lines. Nearly all of the inactive MxA variants exerted a dominant-negative effect on the antiviral function of wild-type MxA, suggesting an MxA null phenotype in heterozygous carriers. Our study provides genetic evidence for a crucial role of the MX1-based antiviral defense in controlling zoonotic IAV infections in humans.


Subject(s)
Influenza A Virus, H7N9 Subtype , Influenza, Human/genetics , Influenza, Human/virology , Myxovirus Resistance Proteins/genetics , Agricultural Workers' Diseases/genetics , Agricultural Workers' Diseases/virology , Animals , Cell Line , Genetic Predisposition to Disease , Genetic Variation , Heterozygote , Humans , Influenza A Virus, H7N9 Subtype/physiology , Influenza A virus/physiology , Mutation, Missense , Myxovirus Resistance Proteins/chemistry , Myxovirus Resistance Proteins/metabolism , Poultry , Viral Zoonoses , Whole Genome Sequencing
20.
Molecules ; 26(13)2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1288963

ABSTRACT

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Catechin/analogs & derivatives , Tea/chemistry , Animals , Antiviral Agents/therapeutic use , Catechin/pharmacology , Catechin/therapeutic use , Humans , Virus Internalization/drug effects , Viruses/drug effects
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