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1.
Nat Commun ; 13(1): 4350, 2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1960369

ABSTRACT

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Neutralization Tests , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
2.
MMWR Morb Mortal Wkly Rep ; 71(29): 913-919, 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1955141

ABSTRACT

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.


Subject(s)
COVID-19 , Influenza A Virus, H5N1 Subtype , Influenza Vaccines , Influenza, Human , Humans , Influenza A Virus, H3N2 Subtype/genetics , Influenza B virus/genetics , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Population Surveillance , SARS-CoV-2 , Seasons , United States/epidemiology
3.
Emerg Infect Dis ; 28(7): 1442-1445, 2022 07.
Article in English | MEDLINE | ID: covidwho-1917186

ABSTRACT

To detect new and changing SARS-CoV-2 variants, we investigated candidate Delta-Omicron recombinant genomes from Centers for Disease Control and Prevention national genomic surveillance. Laboratory and bioinformatic investigations identified and validated 9 genetically related SARS-CoV-2 viruses with a hybrid Delta-Omicron spike protein.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Computational Biology , Humans , SARS-CoV-2/genetics , United States/epidemiology
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330917

ABSTRACT

Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States.

5.
MMWR Morb Mortal Wkly Rep ; 71(6): 206-211, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1687588

ABSTRACT

Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.† The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/genetics , Centers for Disease Control and Prevention, U.S. , Genomics , Humans , Prevalence , Public Health Surveillance/methods , United States/epidemiology
6.
Nat Med ; 28(5): 1083-1094, 2022 05.
Article in English | MEDLINE | ID: covidwho-1671607

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated a clear need for high-throughput, multiplexed and sensitive assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses and their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (mCARMEN), which combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable the identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.


Subject(s)
COVID-19 , Influenza, Human , COVID-19/diagnosis , Humans , Microfluidics , SARS-CoV-2/genetics
7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293462

ABSTRACT

The divergence of SARS-CoV-2 into variants of concern/interest (VOC/VOI) necessitated analysis of their impact on vaccines. Escape from vaccine-induced antibodies by SARS-CoV-2 VOC/VOIs was analyzed to ascertain and rank their risk. The variants showed differential reductions in neutralization and replication titers by the post-vaccination sera with Beta variant showing the most neutralization escape that was mechanistically driven by mutations in both the N-terminal domain and receptor-binding domain of the spike.

9.
MMWR Morb Mortal Wkly Rep ; 70(29): 1013-1019, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1320641

ABSTRACT

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.


Subject(s)
COVID-19/epidemiology , Influenza, Human/epidemiology , Pandemics , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Humans , United States/epidemiology
10.
Clin Infect Dis ; 73(Suppl 1): S77-S80, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315690

ABSTRACT

A suspected outbreak of influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a long-term care facility in Los Angeles County was, months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow Centers for Disease Control and Prevention (CDC) guidelines that specifically address infection control challenges.


Subject(s)
COVID-19 , Influenza, Human , Disease Outbreaks , Humans , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Long-Term Care , SARS-CoV-2
11.
Emerg Infect Dis ; 27(7): 1821-1830, 2021.
Article in English | MEDLINE | ID: covidwho-1278363

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 102.0, influenza B virus at 102.2, and SARS-CoV-2 at 100.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.


Subject(s)
COVID-19 , Influenza A virus , Humans , Influenza A virus/genetics , Influenza B virus/genetics , Multiplex Polymerase Chain Reaction , Reverse Transcription , SARS-CoV-2
12.
Clin Infect Dis ; 73(Suppl 1): S77-S80, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1217832

ABSTRACT

A suspected outbreak of influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a long-term care facility in Los Angeles County was, months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow Centers for Disease Control and Prevention (CDC) guidelines that specifically address infection control challenges.


Subject(s)
COVID-19 , Influenza, Human , Disease Outbreaks , Humans , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Long-Term Care , SARS-CoV-2
13.
Emerg Infect Dis ; 27(5): 1380-1392, 2021 05.
Article in English | MEDLINE | ID: covidwho-1202277

ABSTRACT

Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines.


Subject(s)
COVID-19 , Influenza, Human , Animals , Cats , Cell Line , Dogs , Humans , Mice , Peptidyl-Dipeptidase A , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
14.
Nature ; 592(7852): 122-127, 2021 04.
Article in English | MEDLINE | ID: covidwho-1104508

ABSTRACT

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.


Subject(s)
COVID-19/transmission , COVID-19/virology , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Bronchi/cytology , Bronchi/virology , COVID-19/epidemiology , Cell Line , Cells, Cultured , Cricetinae , Disease Models, Animal , Epithelial Cells/virology , Female , Ferrets/virology , Founder Effect , Gene Knock-In Techniques , Genetic Fitness , Humans , Male , Mesocricetus , Mice , Nasal Mucosa/cytology , Nasal Mucosa/virology , Protein Binding , RNA, Viral/analysis , Receptors, Coronavirus/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
15.
Nature ; 582(7811): 277-282, 2020 06.
Article in English | MEDLINE | ID: covidwho-980299

ABSTRACT

The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples1-3 while simultaneously testing for many pathogens4-6. Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents7 self-organize in a microwell array8 to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health9-11.


Subject(s)
CRISPR-Associated Proteins/metabolism , CRISPR-Cas Systems/genetics , Microfluidic Analytical Techniques/methods , Virus Diseases/diagnosis , Virus Diseases/virology , Animals , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Drug Resistance, Viral/genetics , Genome, Viral/genetics , HIV/classification , HIV/genetics , HIV/isolation & purification , Humans , Influenza A virus/classification , Influenza A virus/genetics , Influenza A virus/isolation & purification , Microfluidic Analytical Techniques/instrumentation , RNA, Guide/genetics , SARS-CoV-2 , Sensitivity and Specificity
16.
bioRxiv ; 2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-915978

ABSTRACT

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic 1 . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

17.
AU-GSB E-Journal ; 13(1):68-89, 2020.
Article in English | ProQuest Central | ID: covidwho-822517

ABSTRACT

Many people in our Developed Western World believe that we are entering or are already in, an era of great societal change, redolent of the Renaissance and the Reformation periods from a cultural perspective and of the Industrial Revolution in terms of commerce, manufacturing industry and service provision. This study reviews and critiques a broad literature of developments from twelve areas namely 1. Loss of spiritual Faith by many;2. Increasing Economic Inequality across the social strata;3.The Increasing Incidence of Mental Illness in Western Societies;4. Increasing Narcotic Drug Addiction;5. Increasing Blue Screen Addiction;6. Failure to Act on Global Warming and Erratic Weather Events;7. Corruption of Democratically Elected Politicians and the resulting Public Protests Against Their Actions;8. Trying to Fix the Symptoms of these maladies rather than the Cause;9.Increasing Civil Unrest Worldwide and Increasing Militarization of Police Forces Worldwide;10. Endocrine Disruptors;11. Profit Before People;12. Corona Virus (Covid 19). A selection of texts by well-established and specialist academic authors testify to the historic concern on these issues. These are supplemented by recent/current on-line sources. Academic Journals are limited to past issues because immediate issues such as Covid -19 and racial issues such as the murder of George Floyd by police officers have yet to be published. This research identifies the unintended social and medical consequences which have arisen, in twelve of the most troubling social and medical issues of today. This research invites reflection and thoughtful critical comment from readers.

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