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1.
J Am Soc Nephrol ; 32(9): 2147-2152, 2021 09.
Article in English | MEDLINE | ID: covidwho-1708655

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in patients with ESKD, and vaccination is hoped to prevent infection. METHODS: Between January 18 and February 24, 2021, 225 kidney transplant recipients (KTRs) and 45 patients on hemodialysis (HDPs) received two injections of mRNA BNT162b2 vaccine. The postvaccinal humoral and cellular response was explored in the first 45 KTRs and ten HDPs. RESULTS: After the second dose, eight HDPs (88.9%) and eight KTRs (17.8%) developed antispike SARS-CoV-2 antibodies (P<0.001). Median titers of antibodies in responders were 1052 AU/ml (IQR, 515-2689) in HDPs and 671 AU/ml (IQR, 172-1523) in KTRs (P=0.40). Nine HDPs (100%) and 26 KTRs (57.8%) showed a specific T cell response (P=0.06) after the second injection. In responders, median numbers of spike-reactive T cells were 305 SFCs per 106 CD3+ T cells (IQR, 95-947) in HDPs and 212 SFCs per 106 CD3+ T cells (IQR, 61-330) in KTRs (P=0.40). In KTRs, the immune response to BNT162b2 seemed influenced by the immunosuppressive regimen, particularly tacrolimus or belatacept. CONCLUSION: Immunization with BNT162b2 seems more efficient in HDPs, indicating that vaccination should be highly recommended in these patients awaiting a transplant. However, the current vaccinal strategy for KTRs may not provide effective protection against COVID-19 and will likely need to be improved.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19 Vaccines/pharmacology , COVID-19/immunology , Kidney Transplantation , Renal Dialysis , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Aged , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cohort Studies , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/therapy , Kidney Transplantation/adverse effects , Male , Middle Aged , Pandemics , RNA, Messenger/genetics , Retrospective Studies , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Transplant Recipients
2.
Br J Nutr ; 127(8): 1172-1179, 2022 04 28.
Article in English | MEDLINE | ID: covidwho-1665637

ABSTRACT

Zn deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This narrative review aims at presenting and discussing functional aspects and possible mechanisms involved in the potential role of Zn in the immune response and antiviral activity for coronavirus infectious disease-19 (COVID-19) prevention and control. The searches were conducted in PubMed and Science Direct databases, using clinical trials, experimental studies in animals and humans, case-control studies, case series, letters to the editor, and review articles published in English, without restrictions on year of publication. Search approach was based on using the terms: 'zinc', 'COVID-19', 'antiviral agents', 'immunologic factors' and 'respiratory tract infections'. Literature shows the importance of Zn as an essential mineral immunomodulator with relevant antiviral activity in the body. Thus, although there is still a scarcity of studies evaluating Zn supplementation in patients with COVID-19, the results on the topic show the necessity of controlling Zn mineral deficiency, as well as maintaining its homoeostasis in the body in order to strengthen the immune system and improve the prevention of highly complex viral infections, such as that of the COVID-19.


Subject(s)
COVID-19 , Communicable Diseases , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Communicable Diseases/drug therapy , Humans , Zinc/therapeutic use
3.
Rev Med Virol ; 31(5): 1-14, 2021 09.
Article in English | MEDLINE | ID: covidwho-1575050

ABSTRACT

Of all the nutrients, vitamin A has been the most extensively evaluated for its impact on immunity. There are three main forms of vitamin A, retinol, retinal and retinoic acid (RA) with the latter being most biologically active and all-trans-RA (ATRA) its main derivative. Vitamin A is a key regulator of the functions of various innate and adaptive immune cells and promotes immune-homeostasis. Importantly, it augments the interferon-based innate immune response to RNA viruses decreasing RNA virus replication. Several clinical trials report decreased mortality in measles and Ebola with vitamin A supplementation.During the Covid-19 pandemic interventions such as convalescent plasma, antivirals, monoclonal antibodies and immunomodulator drugs have been tried but most of them are difficult to implement in resource-limited settings. The current review explores the possibility of mega dose vitamin A as an affordable adjunct therapy for Covid-19 illness with minimal reversible side effects. Insight is provided into the effect of vitamin A on ACE-2 expression in the respiratory tract and its association with the prognosis of Covid-19 patients. Vitamin A supplementation may aid the generation of protective immune response to Covid-19 vaccines. An overview of the dosage and safety profile of vitamin A is presented along with recommended doses for prophylactic/therapeutic use in randomised controlled trials in Covid-19 patients.


Subject(s)
COVID-19/immunology , COVID-19/prevention & control , Vitamin A/administration & dosage , Animals , COVID-19/virology , Humans , Immunity/drug effects , Immunomodulation/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Vitamin A/analysis
4.
Front Vet Sci ; 7: 570748, 2020.
Article in English | MEDLINE | ID: covidwho-1573664

ABSTRACT

The novel coronavirus (SARS-CoV-2) infection (COVID-19) has raised considerable concern on the entire planet. On March 11, 2020, COVID-19 was categorized by the World Health Organization (WHO) as a pandemic infection, and by March 18, 2020, it has spread to 146 countries. The first internal defense line against numerous diseases is personalized immunity. Although it cannot be claimed that personalized nutrition will have an immediate impact on a global pandemic, as the nutritional interventions required a long time to induce beneficial outcomes on immunity development, nutritional strategies are still able to clarify and have a beneficial influence on the interplay between physiology and diet, which could make a positive contribution to the condition in the next period. As such, a specific goal for every practitioner is to evaluate different tests to perceive the status of the patient, such as markers of inflammation, insulin regulation, and nutrient status, and to detect possible imbalances or deficiencies. During the process of disease development, the supplementation and addition of different nutrients and nutraceuticals can influence not only the viral replication but also the cellular mechanisms. It is essential to understand that every patient has its individual needs. Even though many nutrients, nutraceuticals, and drugs have beneficial effects on the immune response and can prevent or ameliorate viral infections, it is essential to detect at what stage in COVID-19 progression the patient is at the moment and decide what kind of nutrition intervention is necessary. Furthermore, understanding the pathogenesis of coronavirus infection is critical to make proper recommendations.

5.
Viral Immunol ; 34(3): 165-173, 2021 04.
Article in English | MEDLINE | ID: covidwho-1569564

ABSTRACT

The current pandemic is caused by the coronavirus disease 2019 (COVID-19), which is, in turn, induced by a novel coronavirus (SARS-CoV-2) that triggers an acute respiratory disease. In recent years, the emergence of SARS-CoV-2 is the third highly pathogenic event and large-scale epidemic affecting the human population. It follows the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. This novel SARS-CoV-2 employs the angiotensin-converting enzyme 2 (ACE2) receptor, like SARS-CoV, and spreads principally in the respiratory tract. The viral spike (S) protein of coronaviruses facilities the attachment to the cellular receptor, entrance, and membrane fusion. The S protein is a glycoprotein and is critical to elicit an immune response. Glycosylation is a biologically significant post-translational modification in virus surface proteins. These glycans play important roles in the viral life cycle, structure, immune evasion, and cell infection. However, it is necessary to search for new information about viral behavior and immunological host's response after SARS-CoV-2 infection. The present review discusses the implications of the CoV-2 S protein glycosylation in the SARS-CoV-2/ACE2 interaction and the immunological response. Elucidation of the glycan repertoire on the spike protein can propel research for the development of an appropriate vaccine.


Subject(s)
Angiotensin-Converting Enzyme 2/physiology , COVID-19/immunology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/physiology , Glycosylation , Humans , SARS-CoV-2/chemistry , SARS-CoV-2/genetics
7.
Angiogenesis ; 24(3): 677-693, 2021 08.
Article in English | MEDLINE | ID: covidwho-1549443

ABSTRACT

Endothelial barrier disruption and vascular leak importantly contribute to organ dysfunction and mortality during inflammatory conditions like sepsis and acute respiratory distress syndrome. We identified the kinase Arg/Abl2 as a mediator of endothelial barrier disruption, but the role of Arg in endothelial monolayer regulation and its relevance in vivo remain poorly understood. Here we show that depletion of Arg in endothelial cells results in the activation of both RhoA and Rac1, increased cell spreading and elongation, redistribution of integrin-dependent cell-matrix adhesions to the cell periphery, and improved adhesion to the extracellular matrix. We further show that Arg is activated in the endothelium during inflammation, both in murine lungs exposed to barrier-disruptive agents, and in pulmonary microvessels of septic patients. Importantly, Arg-depleted endothelial cells were less sensitive to barrier-disruptive agents. Despite the formation of F-actin stress fibers and myosin light chain phosphorylation, Arg depletion diminished adherens junction disruption and intercellular gap formation, by reducing the disassembly of cell-matrix adhesions and cell retraction. In vivo, genetic deletion of Arg diminished vascular leak in the skin and lungs, in the presence of a normal immune response. Together, our data indicate that Arg is a central and non-redundant regulator of endothelial barrier integrity, which contributes to cell retraction and gap formation by increasing the dynamics of adherens junctions and cell-matrix adhesions in a Rho GTPase-dependent fashion. Therapeutic inhibition of Arg may provide a suitable strategy for the treatment of a variety of clinical conditions characterized by vascular leak.


Subject(s)
Extracellular Matrix/metabolism , Gap Junctions/enzymology , Human Umbilical Vein Endothelial Cells/enzymology , Protein-Tyrosine Kinases/metabolism , Pulmonary Alveoli/enzymology , Animals , Cell Adhesion/genetics , Enzyme Activation , Extracellular Matrix/genetics , Gap Junctions/genetics , Humans , Inflammation/enzymology , Inflammation/genetics , Mice , Mice, Knockout , Protein-Tyrosine Kinases/genetics
8.
Pan Afr Med J ; 38: 93, 2021.
Article in French | MEDLINE | ID: covidwho-1547720

ABSTRACT

INTRODUCTION: SARS-CoV-2 serology tests could play a crucial role in estimating the prevalence of COVID-19. The purpose of this study was to estimate the prevalence of COVID-19 among travellers and workers in Bukavu, a city in eastern Democratic Republic of the Congo. METHODS: between May and August 2020, the Cellex qSARS-CoV-2 IgG/IgM Rapid Test (Cellex, Inc., USA), lateral flow immunoassay was used to rapidly detect and differentiate antibodies against SARS-CoV-2 among travellers and workers seeking medical certification. RESULTS: among the 684 residents of the city of Bukavu screened for COVID-19 (4.2% Hispanic, 2.8% other African, 0.9% Asian), the seroprevalence anti-SARS-CoV-2 antibodies was 40.8% (IgG+/IgM+: 34.6%; IgG+/IgM-: 0.5%; IgG-/IgM+: 5.4%). Cumulative seroprevalence of anti-SARS-CoV-2 IgG antibodies increased from 24.5% to 35.2% from May to August 2020. Independent predictors of SARS-CoV-2 antibodies were age > 60 years [adjusted OR = 2.07(1.26-3.38)] and non-membership of the medical staff [adjusted OR = 2.28 (1.22-4.26)]. Thirteen point nine percent of patients seropositive for SARS-CoV-2 antibodies were symptomatic and hospitalized. CONCLUSION: this study shows a very high seroprevalence of SARS-CoV-2 antibodies among travellers and workers in Bukavu, a city in eastern Democratic Republic of the Congo, which may positively affect community immunity in the study population. Thus, the management of COVID-19 should be contextualized according to local realities.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/isolation & purification , Travel , Adult , Age Factors , Aged , COVID-19/diagnosis , Democratic Republic of the Congo/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Immunoassay , Male , Middle Aged , SARS-CoV-2/immunology , Seroepidemiologic Studies
9.
Emerg Microbes Infect ; 10(1): 365-375, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1490458

ABSTRACT

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.


Subject(s)
Hepatitis E/immunology , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Papillomavirus Infections/immunology , Papillomavirus Vaccines/immunology , Vaccines, Synthetic/immunology , Viral Hepatitis Vaccines/immunology , Adolescent , Adult , Aged , Antibodies, Viral/immunology , Female , Hepatitis E/prevention & control , Hepatitis E/virology , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Immunity , Immunoglobulin G/immunology , Male , Middle Aged , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/genetics , Vaccination/adverse effects , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Viral Hepatitis Vaccines/administration & dosage , Viral Hepatitis Vaccines/adverse effects , Viral Hepatitis Vaccines/genetics , Young Adult
10.
Aging Clin Exp Res ; 33(7): 2031-2041, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1491488

ABSTRACT

BACKGROUND: The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has re-ignited interest in the possible role of vitamin D in modulation of host responses to respiratory pathogens. Indeed, vitamin D supplementation has been proposed as a potential preventative or therapeutic strategy. Recommendations for any intervention, particularly in the context of a potentially fatal pandemic infection, should be strictly based on clinically informed appraisal of the evidence base. In this narrative review, we examine current evidence relating to vitamin D and COVID-19 and consider the most appropriate practical recommendations. OBSERVATIONS: Although there are a growing number of studies investigating the links between vitamin D and COVID-19, they are mostly small and observational with high risk of bias, residual confounding, and reverse causality. Extrapolation of molecular actions of 1,25(OH)2-vitamin D to an effect of increased 25(OH)-vitamin D as a result of vitamin D supplementation is generally unfounded, as is the automatic conclusion of causal mechanisms from observational studies linking low 25(OH)-vitamin D to incident disease. Efficacy is ideally demonstrated in the context of adequately powered randomised intervention studies, although such approaches may not always be feasible. CONCLUSIONS: At present, evidence to support vitamin D supplementation for the prevention or treatment of COVID-19 is inconclusive. In the absence of any further compelling data, adherence to existing national guidance on vitamin D supplementation to prevent vitamin D deficiency, predicated principally on maintaining musculoskeletal health, appears appropriate.


Subject(s)
COVID-19 , Vitamin D Deficiency , Humans , SARS-CoV-2 , Vitamin D , Vitamins
11.
Vaccines (Basel) ; 8(3)2020 Sep 22.
Article in English | MEDLINE | ID: covidwho-1438751

ABSTRACT

In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most recently, COVID-19. Therefore, it is important to understand the cellular and molecular mechanisms of action of vaccine adjuvants, which generally trigger the innate immune system to enhance signal transition to adaptive immunity, resulting in pathogen-specific protection. Thus, improved understanding of vaccine adjuvant mechanisms may aid in the design of "intelligent" vaccines to provide robust protection from pathogens. Various commonly used clinical adjuvants, such as aluminium salts, saponins or emulsions, have been identified as activators of inflammasomes - multiprotein signalling platforms that drive activation of inflammatory caspases, resulting in secretion of pro-inflammatory cytokines of the IL-1 family. Importantly, these cytokines affect the cellular and humoral arms of adaptive immunity, which indicates that inflammasomes represent a valuable target of vaccine adjuvants. In this review, we highlight the impact of different inflammasomes on vaccine adjuvant-induced immune responses regarding their mechanisms and immunogenicity. In this context, we focus on clinically relevant adjuvants that have been shown to activate the NLRP3 inflammasome and also present various experimental adjuvants that activate the NLRP3-, NLRC4-, AIM2-, pyrin-, or non-canonical inflammasomes and could have the potential to improve future vaccines. Together, we provide a comprehensive overview on vaccine adjuvants that are known, or suggested, to promote immunogenicity through inflammasome-mediated signalling.

12.
J Clin Invest ; 130(11): 6151-6157, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-1435146

ABSTRACT

Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.


Subject(s)
Betacoronavirus , Complement Membrane Attack Complex , Coronavirus Infections , Extracellular Traps , Neutrophils , Pandemics , Pneumonia, Viral , Thromboplastin , Thrombosis , Aged , Betacoronavirus/immunology , Betacoronavirus/metabolism , COVID-19 , Complement Activation/drug effects , Complement Membrane Attack Complex/immunology , Complement Membrane Attack Complex/metabolism , Coronavirus Infections/blood , Coronavirus Infections/immunology , Extracellular Traps/immunology , Extracellular Traps/metabolism , Female , Humans , Male , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , Peptides, Cyclic/pharmacology , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Receptor, Anaphylatoxin C5a/antagonists & inhibitors , Receptor, Anaphylatoxin C5a/blood , Receptor, Anaphylatoxin C5a/immunology , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Thrombin/immunology , Thrombin/metabolism , Thromboplastin/immunology , Thromboplastin/metabolism , Thrombosis/blood , Thrombosis/immunology , Thrombosis/virology
13.
Res Sq ; 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1417405

ABSTRACT

Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™. While antigen dose had some effect on Fc-effector profiles, both antigen dose and boosting significantly altered overall titers, neutralization and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were strongly associated with distinct levels of protection in the upper and lower respiratory tract, pointing to the presence of combined, but distinct, compartment-specific neutralization and Fc-mechanisms as key determinants of protective immunity against infection. Moreover, NVX-CoV2373 elicited antibodies functionally target emerging SARS-CoV-2 variants, collectively pointing to the critical collaborative role for Fab and Fc in driving maximal protection against SARS-CoV-2. Collectively, the data presented here suggest that a single dose may prevent disease, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.

14.
Front Immunol ; 12: 624293, 2021.
Article in English | MEDLINE | ID: covidwho-1394756

ABSTRACT

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which interacts with a wide range of organic molecules of endogenous and exogenous origin, including environmental pollutants, tryptophan metabolites, and microbial metabolites. The activation of AHR by these agonists drives its translocation into the nucleus where it controls the expression of a large number of target genes that include the AHR repressor (AHRR), detoxifying monooxygenases (CYP1A1 and CYP1B1), and cytokines. Recent advances reveal that AHR signaling modulates aspects of the intrinsic, innate and adaptive immune response to diverse microorganisms. This review will focus on the increasing evidence supporting a role for AHR as a modulator of the host response to viral infection.


Subject(s)
Adaptive Immunity , Immunity, Innate , Receptors, Aryl Hydrocarbon/metabolism , Virus Diseases/virology , Viruses/immunology , Active Transport, Cell Nucleus , Animals , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Ligands , Signal Transduction , Virus Diseases/genetics , Virus Diseases/immunology , Virus Diseases/metabolism , Viruses/genetics , Viruses/pathogenicity
15.
Neurobiol Sleep Circadian Rhythms ; 10: 100063, 2021 May.
Article in English | MEDLINE | ID: covidwho-1386358

ABSTRACT

Night shift work is a risk factor for viral infection, suggesting that night shift schedules compromise host defense mechanisms. Prior studies have investigated changes in the temporal profiles of circulating cytokines important for priming and restraining the immune response to infectious challenges from night shift work, but not by way of a 24-h constant routine of continuous wakefulness devoid of behavioral or environmental influences. Hence the true endogenous pattern of cytokines, and the combined effect of sleep loss and circadian misalignment on these cytokines remains unknown. Here, 14 healthy young men and women underwent three days of either a simulated night shift or a simulated day shift schedule under dim light in a controlled in-laboratory environment. This was followed by a 24-h constant routine protocol during which venous blood was collected at 3-h intervals. Those who had been in the night shift schedule showed lower mean circulating TNF-α (t13 = -6.03, p < 0.001), without any significant differences in IL-1ß, IL-8 and IL-10, compared with those who had been in the day shift (i.e., control) schedule. Furthermore, circulating IL-6 increased with time awake in both shift work conditions (t13 = 6.03, p < 0.001), such that temporal changes in IL-6 were markedly shifted relative to circadian clock time in the night shift condition. These results indicate that night shift work compromises host defense by creating cytokine conditions that initially impede anti-viral immunity (lower TNF-α) and may eventually promote autoimmunity (mistimed rise in IL-6).

16.
Cell Host Microbe ; 29(2): 160-164, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1385266

ABSTRACT

The emergence of alternate variants of SARS-CoV-2 due to ongoing adaptations in humans and following human-to-animal transmission has raised concern over the efficacy of vaccines against new variants. We describe human-to-animal transmission (zooanthroponosis) of SARS-CoV-2 and its implications for faunal virus persistence and vaccine-mediated immunity.


Subject(s)
COVID-19/veterinary , Communicable Diseases, Emerging/veterinary , SARS-CoV-2/pathogenicity , Zoonoses/transmission , Zoonoses/virology , Animals , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , Communicable Diseases, Emerging/transmission , Communicable Diseases, Emerging/virology , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Humans , Immunity , Viral Vaccines/immunology
17.
J Med Virol ; 93(9): 5350-5357, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1384240

ABSTRACT

PARP14 and PARP9 play a key role in macrophage immune regulation. SARS-CoV-2 is an emerging viral disease that triggers hyper-inflammation known as a cytokine storm. In this study, using in silico tools, we hypothesize about the immunological phenomena of molecular mimicry between SARS-CoV-2 Nsp3 and the human PARP14 and PARP9. The results showed an epitope of SARS-CoV-2 Nsp3 protein that contains consensus sequences for both human PARP14 and PARP9 that are antigens for MHC Classes 1 and 2, which can potentially induce an immune response against human PARP14 and PARP9; while its depletion causes a hyper-inflammatory state in SARS-CoV-2 patients.


Subject(s)
COVID-19/immunology , Coronavirus Papain-Like Proteases/chemistry , Cytokine Release Syndrome/immunology , Neoplasm Proteins/chemistry , Poly(ADP-ribose) Polymerases/chemistry , SARS-CoV-2/immunology , Amino Acid Sequence , Binding Sites , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Computer Simulation , Consensus Sequence , Coronavirus Papain-Like Proteases/genetics , Coronavirus Papain-Like Proteases/immunology , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , Gene Expression , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/chemistry , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Macrophages/immunology , Macrophages/virology , Molecular Docking Simulation , Molecular Mimicry , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/immunology , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Sequence Alignment , Sequence Homology, Amino Acid , Thermodynamics
18.
Viruses ; 13(1)2021 Jan 16.
Article in English | MEDLINE | ID: covidwho-1389525

ABSTRACT

Our recent study identified seven key microRNAs (miR-8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) similar between SARS-CoV-2 and the human genome, pointing at miR-related mechanisms in viral entry and the regulatory effects on host immunity. To identify the putative roles of these miRs in zoonosis, we assessed their conservation, compared with humans, in some key wild and domestic animal carriers of zoonotic viruses, including bat, pangolin, pig, cow, rat, and chicken. Out of the seven miRs under study, miR-3611 was the most strongly conserved across all species; miR-5197 was the most conserved in pangolin, pig, cow, bat, and rat; miR-1307 was most strongly conserved in pangolin, pig, cow, bat, and human; miR-3691-3p in pangolin, cow, and human; miR-3934-3p in pig and cow, followed by pangolin and bat; miR-1468 was most conserved in pangolin, pig, and bat; while miR-8066 was most conserved in pangolin and pig. In humans, miR-3611 and miR-1307 were most conserved, while miR-8066, miR-5197, miR-3334-3p and miR-1468 were least conserved, compared with pangolin, pig, cow, and bat. Furthermore, we identified that changes in the miR-5197 nucleotides between pangolin and human can generate three new miRs, with differing tissue distribution in the brain, lung, intestines, lymph nodes, and muscle, and with different downstream regulatory effects on KEGG pathways. This may be of considerable importance as miR-5197 is localized in the spike protein transcript area of the SARS-CoV-2 genome. Our findings may indicate roles for these miRs in viral-host co-evolution in zoonotic hosts, particularly highlighting pangolin, bat, cow, and pig as putative zoonotic carriers, while highlighting the miRs' roles in KEGG pathways linked to viral pathogenicity and host responses in humans. This in silico study paves the way for investigations into the roles of miRs in zoonotic disease.


Subject(s)
Biological Coevolution , MicroRNAs/genetics , SARS-CoV-2/genetics , Animals , COVID-19/transmission , COVID-19/virology , Chickens , Gene Regulatory Networks , Genome/genetics , Host Specificity , Humans , Mammals , MicroRNAs/chemistry , MicroRNAs/metabolism , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Sequence Alignment , Tissue Distribution , Zoonoses/transmission , Zoonoses/virology
19.
Mol Biol Evol ; 38(2): 702-715, 2021 01 23.
Article in English | MEDLINE | ID: covidwho-1387955

ABSTRACT

Despite SARS-CoV and SARS-CoV-2 being equipped with highly similar protein arsenals, the corresponding zoonoses have spread among humans at extremely different rates. The specific characteristics of these viruses that led to such distinct outcomes remain unclear. Here, we apply proteome-wide comparative structural analysis aiming to identify the unique molecular elements in the SARS-CoV-2 proteome that may explain the differing consequences. By combining protein modeling and molecular dynamics simulations, we suggest nonconservative substitutions in functional regions of the spike glycoprotein (S), nsp1, and nsp3 that are contributing to differences in virulence. Particularly, we explain why the substitutions at the receptor-binding domain of S affect the structure-dynamics behavior in complexes with putative host receptors. Conservation of functional protein regions within the two taxa is also noteworthy. We suggest that the highly conserved main protease, nsp5, of SARS-CoV and SARS-CoV-2 is part of their mechanism of circumventing the host interferon antiviral response. Overall, most substitutions occur on the protein surfaces and may be modulating their antigenic properties and interactions with other macromolecules. Our results imply that the striking difference in the pervasiveness of SARS-CoV-2 and SARS-CoV among humans seems to significantly derive from molecular features that modulate the efficiency of viral particles in entering the host cells and blocking the host immune response.


Subject(s)
Molecular Dynamics Simulation , Proteomics , SARS Virus/chemistry , SARS Virus/pathogenicity , SARS-CoV-2/chemistry , SARS-CoV-2/pathogenicity , Viral Proteins/chemistry , Animals , Humans , Protein Domains , SARS Virus/metabolism , SARS-CoV-2/metabolism , Species Specificity , Viral Proteins/metabolism
20.
Cardiovasc Res ; 117(1): 224-239, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1387842

ABSTRACT

AIMS: To elucidate the prognostic role of monocytes in the immune response of patients with coronary artery disease (CAD) at risk for life-threatening heart and lung injury as major complications of SARS-CoV-2 infection. METHODS AND RESULTS: From February to April 2020, we prospectively studied a cohort of 96 participants comprising 47 consecutive patients with CAD and acute SARS-CoV-2 infection (CAD + SARS-CoV-2), 19 CAD patients without infections, and 30 healthy controls. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 h of admission. Respiratory failure was stratified by the Horovitz Index (HI) as moderately/severely impaired when HI ≤200 mmHg. The clinical endpoint (EP) was defined as HI ≤200 mmHg with subsequent mechanical ventilation within a follow-up of 30 days. The numbers of CD14dimCD16+ non-classical monocytes in peripheral blood were remarkably low in CAD + SARS-CoV-2 compared with CAD patients without infection and healthy controls (P < 0.0001). Moreover, these CD14dimCD16 monocytes showed decreased expression of established markers of adhesion, migration, and T-cell activation (CD54, CD62L, CX3CR1, CD80, and HLA-DR). Decreased numbers of CD14dimCD16+ monocytes were associated with the occurrence of EP. Kaplan-Meier curves illustrate that CAD + SARS-CoV-2 patients with numbers below the median of CD14dimCD16+ monocytes (median 1443 cells/mL) reached EP significantly more often compared to patients with numbers above the median (log-rank 5.03, P = 0.025). CONCLUSION: Decreased numbers of CD14dimCD16+ monocytes are associated with rapidly progressive respiratory failure in CAD + SARS-CoV-2 patients. Intensified risk assessments comprising monocyte sub- and phenotypes may help to identify patients at risk for respiratory failure.


Subject(s)
COVID-19/complications , Coronary Artery Disease/complications , Lipopolysaccharide Receptors/analysis , Monocytes/physiology , Receptors, IgG/analysis , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/immunology , Coronary Artery Disease/immunology , Female , GPI-Linked Proteins/analysis , Humans , Immunohistochemistry , Male , Middle Aged , Monocytes/immunology , Phenotype , Retrospective Studies
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