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1.
Ann Med ; 54(1): 3189-3200, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2106905

Реферат

INTRODUCTION: In order to identify therapeutic targets in Coronavirus disease 2019 (COVID-19), it is important to identify molecules involved in the biological responses that are modulated in COVID-19. Lysophosphatidic acids (LPAs) are involved in the pulmonary inflammation and fibrosis are one of the candidate molecules. The aim of this study was to evaluate the association between the serum levels of autotaxin (ATX), which are enzymes involved in the synthesis of lysophosphatidic acids. MATERIAL AND METHODS: We enrolled 134 subjects with COVID-19 and 58 normal healthy subjects for the study. We measured serum ATX levels longitudinally in COVID-19 patients and investigated the time course and the association with severity and clinical parameters. RESULTS: The serum ATX levels were reduced in all patients with COVID-19, irrespective of the disease severity, and were negatively associated with the serum CRP, D-dimer, and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels. DISCUSSION: Considering the biological properties of LPAs in the pulmonary inflammation and fibrosis, modulation of ATX might be compensatory biological responses to suppress immunological overreaction especially in the lung, which is an important underlying mechanism for the mortality of the disease. CONCLUSIONS: COVID-19 patients showed a decrease in the serum levels of ATX, irrespective of the disease severity. Key MessagesAutotaxin (ATX) is an enzyme involved in the synthesis of lysophosphatidic acid (LPA), which has been reported to be involved in pulmonary inflammation and fibrosis. Patients with COVID-19 show decrease in the serum levels of ATX. Modulation of ATX might be compensatory biological responses to suppress immunological overreaction.


Тема - темы
COVID-19 , Phosphoric Diester Hydrolases , Humans , COVID-19/blood , Fibrosis , Lung , Lysophospholipids , Phosphoric Diester Hydrolases/blood , SARS-CoV-2
2.
Ann Med ; 54(1): 2875-2884, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2106904

Реферат

BACKGROUND: Since the emergence of the novel corona virus (SARS-Cov-2) in the late 2019 and not only the endoscopy practice and training but also the health care systems around the globe suffers. This systematic review focused the impact of Corona Virus Disease (COVID-19) on the endoscopy practice. METHODS: A web search of different databases combining different search terms describing the endoscopy practice and the COVID-19 pandemic was done. Articles were screened for selection of relevant articles in two steps: title and abstract step and full-text screening step, by two independent reviewers and any debate was solved by a third reviewer. RESULTS: Final studies included in qualitative synthesis were 47. The data shown in the relevant articles were evident for marked reduction in the volume of endoscopy, marked affection of colorectal cancer screening, impairments in the workflow, deficiency in personal protective equipment (PPE) and increased likelihood of catching the infection among both the staff and the patients. CONCLUSION: The main outcomes from this review are rescheduling of endoscopy procedures to be suitable with the situation of COVID-19 pandemic in each Country. Also, the endorsement of the importance of PPE use for health care workers and screening of COVID-19 infection pre-procedure.Key messagesThe data focussing Gastrointestinal Endoscopy and COVID-19 emerged from different areas around the globe. The data presented on the published studies were heterogeneous. However, there were remarkable reductions in the volume of GI endoscopy worldwideStaff reallocation added a burden to endoscopy practiceThere was a real risk for COVID-19 spread among both the staff and the patients.


Тема - темы
COVID-19 , Pandemics , Humans , Pandemics/prevention & control , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , Infection Control , Endoscopy, Gastrointestinal
3.
Commun Biol ; 5(1): 1188, 2022 Nov 05.
Статья в английский | MEDLINE | ID: covidwho-2106511

Реферат

SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use.


Тема - темы
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/genetics , SARS-CoV-2/genetics , Glycosylation , Peptidyl-Dipeptidase A , Protein Binding
4.
Commun Biol ; 5(1): 1179, 2022 Nov 04.
Статья в английский | MEDLINE | ID: covidwho-2106510

Реферат

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.


Тема - темы
COVID-19 , Coronavirus 229E, Human , Humans , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2 , Antigens, Viral , Epitopes , Antibodies, Neutralizing
5.
Commun Biol ; 5(1): 1170, 2022 Nov 03.
Статья в английский | MEDLINE | ID: covidwho-2106509

Реферат

The trimeric spike (S) glycoprotein, which protrudes from the SARS-CoV-2 viral envelope, binds to human ACE2, initiated by at least one protomer's receptor binding domain (RBD) switching from a "down" (closed) to an "up" (open) state. Here, we used large-scale molecular dynamics simulations and two-dimensional replica exchange umbrella sampling calculations with more than a thousand windows and an aggregate total of 160 µs of simulation to investigate this transition with and without glycans. We find that the glycosylated spike has a higher barrier to opening and also energetically favors the down state over the up state. Analysis of the S-protein opening pathway reveals that glycans at N165 and N122 interfere with hydrogen bonds between the RBD and the N-terminal domain in the up state, while glycans at N165 and N343 can stabilize both the down and up states. Finally, we estimate how epitope exposure for several known antibodies changes along the opening path. We find that the BD-368-2 antibody's epitope is continuously exposed, explaining its high efficacy.


Тема - темы
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Peptidyl-Dipeptidase A , Polysaccharides , Epitopes
7.
Prim Health Care Res Dev ; 23: e67, 2022 Nov 04.
Статья в английский | MEDLINE | ID: covidwho-2106285

Реферат

BACKGROUND: The coronavirus disease 2019 (COVID-19) has spread rapidly around the world since the initial outbreak in Wuhan, China. With the emergence of the Omicron variant, South Africa is presently the epicentre of the COVID-19 pandemic in sub-Saharan Africa. Healthcare workers have been at the forefront of the pandemic in terms of screening, early detection and clinical management of suspected and confirmed COVID-19 cases. Since the beginning of the outbreak, little has been reported on how healthcare workers have experienced the COVID-19 pandemic in South Africa, particularly within a low-income, rural primary care context. METHODS: The purpose of the present qualitative study design was to explore primary healthcare practitioners' experiences regarding the COVID-19 pandemic at two selected primary healthcare facilities within a low-income rural context in KwaZulu-Natal, South Africa. Data were collected from a purposive sample of 15 participants, which consisted of nurses, physiotherapists, pharmacists, community caregivers, social workers and clinical associates. The participants were both men and women who were all above the age of 20. Data were collected through individual, in-depth face-to-face interviews using a semi-structured interview guide. Audio recordings were transcribed verbatim. Data were analysed manually by thematic analysis following Tech's steps of data analysis. RESULTS: Participants reported personal, occupational and community-related experiences related to the COVID-19 pandemic in South Africa. Personal experiences of COVID-19 yielded superordinate themes of psychological distress, self-stigma, disruption of the social norm, Epiphany and conflict of interest. Occupational experiences yielded superordinate themes of staff infections, COVID-19-related courtesy stigma, resource constraints and poor dissemination of information. Community-related experiences were related to struggles with societal issues, clinician-patient relations and COVID-19 mismanagement of patients. CONCLUSION: The findings of this study suggest that primary healthcare practitioners' experiences around COVID-19 are attributed to the catastrophic effects of the COVID-19 pandemic with the multitude of psychosocial consequences forming the essence of these experiences. Ensuring availability of reliable sources of information regarding the pandemic as well as psychosocial support could be valuable in helping healthcare workers cope with living and working during the pandemic.


Тема - темы
COVID-19 , Pandemics , Male , Humans , Female , Pandemics/prevention & control , COVID-19/epidemiology , South Africa/epidemiology , SARS-CoV-2 , Health Personnel/psychology , Qualitative Research , Primary Health Care
8.
Epidemiol Infect ; 150: e177, 2022 Oct 19.
Статья в английский | MEDLINE | ID: covidwho-2106269

Реферат

Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0-16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24-144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-value<0.0001). Seropositivity increased for all age groups, except for the age group of 0-1 year (P-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12-16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12-16 years [32.2 COI (7-77.1) vs. 11.4 COI(2.8-50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.


Тема - темы
COVID-19 , SARS-CoV-2 , Adolescent , Child , Humans , Infant , Infant, Newborn , Male , Antibodies, Viral , COVID-19/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Prospective Studies , Seroepidemiologic Studies , Female , Child, Preschool
9.
Lancet Healthy Longev ; 3(10): e715-e721, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2106237

Реферат

Both myeloid cells, which contribute to innate immunity, and lymphoid cells, which dominate adaptive immunity, partake in defending against SARS-CoV-2. In response to the virus, the otherwise slow haematopoietic production supply chain quickly unleashes its preconfigured myeloid element, which largely resists a bullwhip-like effect. By contrast, the lymphoid element risks a bullwhip-like effect when it produces T cells and B cells that are specifically designed to clear the virus. As T-cell production is telomere-length dependent and telomeres shorten with age, older adults are at higher risk of a T-cell shortfall when contracting SARS-CoV-2 than are younger adults. A poorly calibrated adaptive immune response, stemming from a bullwhip-like effect, compounded by a T-cell deficit, might thus contribute to the propensity of people with inherently short T-cell telomeres to develop severe COVID-19. The immune systems of these individuals might also generate an inadequate T-cell response to anti-SARS-CoV-2 vaccination.


Тема - темы
COVID-19 , SARS-CoV-2 , Adaptive Immunity , Aged , Humans , SARS-CoV-2/genetics , T-Lymphocytes , Telomere/genetics
11.
STAR Protoc ; 3(4): 101802, 2022 Dec 16.
Статья в английский | MEDLINE | ID: covidwho-2106168

Реферат

Here, we present a protocol to characterize the antiviral ability of a protein of interest to SARS-CoV-2 infection in cultured cells, using MUC1 as an example. We use SARS-CoV-2 ΔN trVLP system, which utilizes transcription and replication-competent SARS-CoV-2 virus-like particles lacking nucleocapsid gene. We describe the optimized procedure to analyze protein interference of viral attachment and entry into cells, and qRT-PCR-based quantification of viral infection. The protocol can be applied to characterize more antiviral candidates and clarify their functioning stage. For complete details on the use and execution of this protocol, please refer to Lai et al. (2022).


Тема - темы
COVID-19 , Humans , SARS-CoV-2 , Nucleocapsid , Cell Line , Antiviral Agents/pharmacology
12.
STAR Protoc ; 3(4): 101794, 2022 Dec 16.
Статья в английский | MEDLINE | ID: covidwho-2106167

Реферат

Discovery of efficacious antiviral agents targeting SARS-CoV-2 main protease (Mpro) is of the highest importance to fight against COVID-19. Here, we describe a simple protocol for high-throughput screening of Mpro inhibitors using a robust fluorescence polarization (FP) assay. Candidate Mpro inhibitors from large compound libraries could be rapidly identified by monitoring the change of millipolarization unit value. This affordable FP assay can be modified to screen antiviral agents targeting virus protease. For complete details on the use and execution of this protocol, please refer to Li et al. (2022), Yan et al. (2021), and Yan et al. (2022c).


Тема - темы
COVID-19 , High-Throughput Screening Assays , Humans , COVID-19/drug therapy , SARS-CoV-2 , Viral Nonstructural Proteins , Cysteine Endopeptidases , Protease Inhibitors/pharmacology , Antiviral Agents/pharmacology , Fluorescence Polarization
13.
Vaccine ; 40(46): 6616-6624, 2022 Nov 02.
Статья в английский | MEDLINE | ID: covidwho-2106125

Реферат

INTRODUCTION: Brazil experienced moments of collapse in its health system throughout 2021, driven by the emergence of variants of concern (VOC) combined with an inefficient initial vaccination strategy against Covid-19. OBJECTIVES: To support decision-makers in formulating COVID-19 immunization policy in the context of limited vaccine availability and evolving variants over time, we evaluate optimal strategies for Covid-19 vaccination in Brazil in 2021, when vaccination was rolled out during Gamma variant predominance. METHODS: Using a discrete-time epidemic model we estimate Covid-19 deaths averted, considering the currently Covid-19 vaccine products and doses available in Brazil; vaccine coverage by target population; and vaccine effectiveness estimates. We evaluated a 5-month time horizon, from early August to the end of December 2021. Optimal vaccination strategies compared the outcomes in terms of averted deaths when varying dose intervals from 8 to 12 weeks, and choosing the minimum coverage levels per age group required prior to expanding vaccination to younger target populations. We also estimated dose availability required over time to allow the implementation of optimal strategies. RESULTS: To maximize the number of averted deaths, vaccine coverage of at least 80 % should be reached in older age groups before starting vaccination into subsequent younger age groups. When evaluating varying dose intervals for AZD1222, reducing the dose interval from 12 to 8 weeks for the primary schedule would result in fewer COVID-19 deaths, but this can only be implemented if accompanied by an increase in vaccine supply of at least 50 % over the coming six-months in Brazil. CONCLUSION: Covid-19 immunization strategies should be tailored to local vaccine product availability and supply over time, circulating variants of concern, and vaccine coverage in target population groups. Modelling can provide valuable and timely evidence to support the implementation of vaccination strategies considering the local context, yet following international and regional technical evidence-based guidance.


Тема - темы
COVID-19 , Vaccines , Humans , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , SARS-CoV-2 , Brazil/epidemiology , ChAdOx1 nCoV-19 , Vaccination
14.
Vaccine ; 40(46): 6664-6669, 2022 Nov 02.
Статья в английский | MEDLINE | ID: covidwho-2106124

Реферат

BACKGROUND: Elderly people in long-term care facilities (LTCF) are at higher risk for (severe) COVID-19, yet evidence of vaccine effectiveness (VE) in this population is scarce. In November 2021 (Delta period), a COVID-19 outbreak occurred at a LTCF in the Netherlands, continuing despite measures and booster vaccination campaign. We investigated the outbreak to assess VE of primary COVID-19 vaccination against SARS-CoV-2 infection and mortality, and to describe the impact of the booster vaccination. METHODS: We calculated attack rate (AR) and case fatality (CF) per vaccination status (unvaccinated, primarily vaccinated and boostered). We calculated VE - at on average 6 months after vaccination - as 1- risk ratio (RR) using the crude risk ratio (RR) with 95% confidence intervals (CI) for the association between vaccination status (primary vaccination versus unvaccinated) and outcomes (SARS-CoV-2 infection and mortality < 30 days after testing positive for SARS-CoV-2). RESULTS: The overall AR was 67% (70/105). CF was 33% (2/6) among unvaccinated cases, 12% among primarily vaccinated (7/58) and 0% (0/5) among boostered. The VE of primary vaccination was 17% (95% CI -28%; 46%) against SARS-CoV-2 infection and 70% (95% CI -44%; 96%) against mortality. Among boostered residents (N = 55), there were 25 cases in the first week after receiving the booster dose, declining to 5 in the second and none in the third week. CONCLUSION: VE of primary vaccination in residents of LTCF was very low against SARS-CoV-2 infection and moderate against mortality. There were few cases at 2 weeks after the booster dose and no deaths, despite the presence of susceptible residents. These data are consistent with the positive impact of the booster vaccination in curbing transmission. Timely booster vaccination in residents of LTCF is therefore important.


Тема - темы
COVID-19 , Humans , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Vaccine Efficacy , SARS-CoV-2 , Immunization Programs , Disease Outbreaks/prevention & control
15.
Prim Care ; 49(4): 609-619, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2105732

Реферат

During the COVID-19 pandemic, providers and patients explored the use of telehealth on a wide and rapid scale. Reflecting on how prenatal providers and pregnant patients used telehealth during the pandemic and afterward, we review existing and new lessons learned from the pandemic. This article summarizes international and national guidelines on prenatal care, presents practice examples on how telehealth and remote patient monitoring were used during the COVID-19 pandemic, and offers lessons learned and suggestions for future care.


Тема - темы
COVID-19 , Telemedicine , Pregnancy , Female , Humans , Pandemics , Prenatal Care , SARS-CoV-2
16.
Pediatr Clin North Am ; 69(3): 547-571, 2022 06.
Статья в английский | MEDLINE | ID: covidwho-2105692

Реферат

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. More than 5 million children have been infected in the United States. Risk factors for more severe disease progression include obesity, pulmonary disease, gastrointestinal disorders, and neurologic comorbidities. Children with COVID-19 are admitted to the pediatric intensive care unit because of severe acute COVID-19 illness or COVID-19-associated multisystem inflammatory syndrome in children. The delta surge of 2021 was responsible for an increased disease burden in children and points to the key role of vaccinating children against this sometimes-deadly disease.


Тема - темы
COVID-19 , COVID-19/complications , COVID-19/epidemiology , Child , Humans , Intensive Care Units, Pediatric , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , United States/epidemiology
18.
Mult Scler Relat Disord ; 67: 104175, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2105622

Реферат

BACKGROUND: Clinical onset of multiple sclerosis (MSpostvacc) and myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGADpostvacc) has been reported in association with SARS-CoV-2-vaccination. There is uncertainty as to whether this is causality (denovo disease) or temporal coincidence (manifestation of a preexisting, subclinical neuroinflammation). OBJECTIVES: Comparing the clinical characteristics of MSpostvacc-patients versus patients with MS (PwMS) whose clinical onset occurred independently of vaccination (MSreference). METHODS: Consecutive patients with clinical onset ≤30 days after SARS-CoV-2-vaccination were included. Clinical data, cerebrospinal fluid (CSF) parameters and magnetic resonance imaging (MRI) as well as optical coherence tomography (OCT) data were compared to an age- and sex-matched MSreference-cohort. RESULTS: We identified 5 MSpostvacc and 1 MOGADpostvacc patients who developed their clinical onset ≤ 30 days after SARS-CoV-2-vaccination. Clinical characteristics, CSF, MRI and OCT parameters from MSpostvacc patients were comparable to the MSreference cohort and showed evidence of preexisting subclinical CNS disease. The single case with MOGADpostvacc clearly differed from PwMS in higher CSF cell counts, remission of MRI lesions during follow-up, and absence of oligoclonal bands. CONCLUSIONS: Our case series indicates that MSpostvacc patients showed a rather typical initial manifestation in temporal association with SARS-CoV-2-vaccination and harbored preexisting subclinical neuroinflammation. This argues against the denovo development of MS in this cohort.


Тема - темы
COVID-19 Vaccines , COVID-19 , Demyelinating Diseases , Multiple Sclerosis , Humans , Autoantibodies , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Demyelinating Diseases/chemically induced , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/cerebrospinal fluid , SARS-CoV-2 , Vaccination/adverse effects
19.
Mult Scler Relat Disord ; 67: 104172, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2105621

Реферат

Multiple sclerosis (MS) is an incurable autoimmune disease known to cause widespread demyelinating lesions in the central nervous system (CNS) and a host of debilitating symptoms in patients. The development of MS is believed to be driven by the breakdown of the blood brain barrier, subsequent infiltration by CD4+ and CD8+ T cells, and widespread CNS inflammation and demyelination. Disease modifying therapies (DMTs) profoundly disrupt these processes and therefore compose an essential component of disease management. However, the effects of these therapeutic agents on vaccine safety and immunogenicity in individuals with MS are not yet fully understood. As such, the primary objective of this review article was to summarize the findings of recently conducted studies on vaccine safety and immunogenicity in MS patients treated with DMTs, particularly in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Discussed in this review are vaccinations against influenza, yellow fever, human papillomavirus, measles, mumps, rubella, Streptococcus pneumoniae, hepatitis B, and COVID-19. This article additionally reviews our current understanding of COVID-19 severity and incidence in this patient population, the risks and benefits of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccination guidelines set forth by MS societies and organizations.


Тема - темы
COVID-19 Vaccines , COVID-19 , Multiple Sclerosis , Humans , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , Multiple Sclerosis/epidemiology , SARS-CoV-2 , Vaccination/adverse effects , COVID-19 Vaccines/adverse effects
20.
Life Sci ; 301: 120624, 2022 Jul 15.
Статья в английский | MEDLINE | ID: covidwho-2105537

Реферат

AIMS: To study effects on cellular innate immune responses to ORF8, ORF10, and Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, in combination with cannabidiol (CBD). MAIN METHODS: HEK293 cells transfected with plasmids expressing control vector, ORF8, ORF10, or M protein were assayed for cell number and markers of apoptosis at 24 h, and interferon and interferon-stimulated gene expression at 14 h, with or without CBD. Cells transfected with polyinosinic:polycytidylic acid (Poly (I:C)) were also studied as a general model of RNA-type viral infection. KEY FINDINGS: Reduced cell number and increased early and late apoptosis were found when expression of viral genes was combined with 1-2 µM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. In cells expressing viral genes, CBD augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2'-5'-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL. CBD also augmented expression of these genes in control cells not expressing viral genes, but without enhancing apoptosis. CBD similarly enhanced the cellular anti-viral response to Poly (I:C). SIGNIFICANCE: Our results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but an augmented innate anti-viral response to these genes in the presence of CBD. Thus, CBD may prime components of the innate immune system, increasing readiness to respond to RNA-type viral infection without activating apoptosis, and could be studied for potential in prophylaxis.


Тема - темы
COVID-19 , Cannabidiol , Antiviral Agents , Apoptosis , Cannabidiol/pharmacology , HEK293 Cells , Humans , Immunity, Innate/genetics , Interferons/pharmacology , Membrane Proteins , Poly I-C/pharmacology , RNA , SARS-CoV-2
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