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1.
Nat Commun ; 14(1): 2308, 2023 04 21.
Article in English | MEDLINE | ID: covidwho-2304491

ABSTRACT

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (~30 kb). Here, we present a plasmid-based viral genome assembly and rescue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.


Subject(s)
COVID-19 , Coronavirus Nucleocapsid Proteins , SARS-CoV-2 , Animals , Coronavirus Nucleocapsid Proteins/genetics , Genome, Viral/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics
2.
Allergy Asthma Proc ; 42(6): 495-505, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1606039

ABSTRACT

Background: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated the worst global pandemic in a century, which has caused millions of infections and deaths as well as massive economic repercussions. Objective: As with any pathogenic virus, it is crucial to understand its unique interactions with the human immune system so that pharmaceutical and prophylactic interventions can be deployed to effectively control the pandemic. Methods: A literature search by using PubMed was conducted in 2020 with variants of the terms "COVID-19," "SARS-CoV-2," and "immunological response." English language articles that presented original data about the immunologic response to coronavirus disease 2019 (COVID-19) were selected for review. This article reviewed the current understanding of the innate and adaptive immune responses to SARS-CoV-2 infection, including their relationship to current therapeutic and diagnostic strategies. Results: SARS-CoV-2 uses several unique molecular techniques to evade detection by the innate immune system early in the course of infection, and upregulation of these innate immune pathways may possibly accelerate the time to recovery and prevent severe disease. Although the majority of cases results in the patients' recovery, a significant proportion of infections result in deaths prompted by the host's inflammatory overreaction to the infection, a response that can be attenuated with corticosteroids and potentially other immune modulators. Conclusion: Current work by the scientific community to further understand how SARS-CoV-2 interacts with the human immune system will be invaluable to our response and preparedness for future coronavirus pandemics.


Subject(s)
Adaptive Immunity , COVID-19 , Immune System , Immunity, Innate , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Disease Susceptibility , Humans , Pandemics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus
3.
J Acad Nutr Diet ; 121(12): 2524-2535, 2021 12.
Article in English | MEDLINE | ID: covidwho-1032438

ABSTRACT

During the current coronavirus disease 2019 (COVID-19) pandemic, health care practices have shifted to minimize virus transmission, with unprecedented expansion of telehealth. This study describes self-reported changes in registered dietitian nutritionist (RDN) practice related to delivery of nutrition care via telehealth shortly after the onset of the COVID-19 pandemic in the United States. This cross-sectional, anonymous online survey was administered from mid-April to mid-May 2020 to RDNs in the United States providing face-to-face nutrition care prior to the COVID-19 pandemic. This survey included 54 questions about practitioner demographics and experience and current practices providing nutrition care via telehealth, including billing procedures, and was completed by 2016 RDNs with a median (interquartile range) of 15 (6-27) years of experience in dietetics practice. Although 37% of respondents reported that they provided nutrition care via telehealth prior to the COVID-19 pandemic, this proportion was 78% at the time of the survey. Respondents reported spending a median (interquartile range) of 30 (20-45) minutes in direct contact with the individual/group per telehealth session. The most frequently reported barriers to delivering nutrition care via telehealth were lack of client interest (29%) and Internet access (26%) and inability to conduct or evaluate typical nutrition assessment or monitoring/evaluation activities (28%). Frequently reported benefits included promoting compliance with social distancing (66%) and scheduling flexibility (50%). About half of RDNs or their employers sometimes or always bill for telehealth services, and of those, 61% are sometimes or always reimbursed. Based on RDN needs, the Academy of Nutrition and Dietetics continues to advocate and provide resources for providing effective telehealth and receiving reimbursement via appropriate coding and billing. Moving forward, it will be important for RDNs to participate fully in health care delivered by telehealth and telehealth research both during and after the COVID-19 public health emergency.


Subject(s)
COVID-19/epidemiology , Nutrition Therapy/methods , Nutrition Therapy/statistics & numerical data , Nutritionists/statistics & numerical data , SARS-CoV-2 , Telemedicine/statistics & numerical data , Cross-Sectional Studies , Delivery of Health Care/economics , Delivery of Health Care/methods , Delivery of Health Care/statistics & numerical data , Dietetics/methods , Dietetics/statistics & numerical data , Humans , Nutritionists/economics , Reimbursement Mechanisms/economics , Reimbursement Mechanisms/statistics & numerical data , Surveys and Questionnaires , Telemedicine/economics , Telemedicine/methods , United States/epidemiology
4.
Cell ; 183(6): 1496-1507.e16, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-898561

ABSTRACT

Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection are not well defined. We charted longitudinal antibody responses to SARS-CoV-2 in 92 subjects after symptomatic COVID-19. Antibody responses to SARS-CoV-2 are unimodally distributed over a broad range, with symptom severity correlating directly with virus-specific antibody magnitude. Seventy-six subjects followed longitudinally to ∼100 days demonstrated marked heterogeneity in antibody duration dynamics. Virus-specific IgG decayed substantially in most individuals, whereas a distinct subset had stable or increasing antibody levels in the same time frame despite similar initial antibody magnitudes. These individuals with increasing responses recovered rapidly from symptomatic COVID-19 disease, harbored increased somatic mutations in virus-specific memory B cell antibody genes, and had persistent higher frequencies of previously activated CD4+ T cells. These findings illuminate an efficient immune phenotype that connects symptom clearance speed to differential antibody durability dynamics.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , CD4-Positive T-Lymphocytes/immunology , COVID-19 , Immunoglobulin G/immunology , Lymphocyte Activation , Mutation , COVID-19/genetics , COVID-19/immunology , Humans , SARS-CoV-2/genetics , SARS-CoV-2/immunology
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