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1.
Mol Med ; 27(1): 162, 2021 12 27.
Article in English | MEDLINE | ID: covidwho-1582120

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel type b coronavirus responsible for the COVID-19 pandemic. With over 224 million confirmed infections with this virus and more than 4.6 million people dead because of it, it is critically important to define the immunological processes occurring in the human response to this virus and pathogenetic mechanisms of its deadly manifestation. This perspective focuses on the contribution of the recently discovered interaction of SARS-CoV-2 Spike protein with neuropilin 1 (NRP1) receptor, NRP1 as a virus entry receptor for SARS-CoV-2, its role in different physiologic and pathologic conditions, and the potential to target the Spike-NRP1 interaction to combat virus infectivity and severe disease manifestations.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Neuropilin-1/chemistry , Neuropilin-1/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/epidemiology , COVID-19/etiology , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/virology , Female , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Infant , Molecular Targeted Therapy/methods , Neuropilin-1/immunology , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism
2.
Front Immunol ; 12: 774776, 2021.
Article in English | MEDLINE | ID: covidwho-1581334

ABSTRACT

Both RNA N6-methyladenosine (m6A) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the m6A methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher m6A modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4+ T cells. Two clusters were identified by unsupervised clustering, m6A cluster A characterized by T cell activation had a higher prognosis than m6A cluster B. Elevated metabolism level, blockage of the immune checkpoint, and lower level of m6A score were observed in m6A cluster B. A protective model was constructed based on nine selected genes and it exhibited an excellent predictive value in COVID-19. Further analysis revealed that the protective score was positively correlated to HFD45 and ventilator-free days, while negatively correlated to SOFA score, APACHE-II score, and crp. Our works systematically depicted a complicated correlation between m6A methylation modification and host lymphocytes in patients infected with SARS-CoV-2 and provided a well-performing model to predict the patients' outcomes.


Subject(s)
Adenosine/analogs & derivatives , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions/immunology , Leukocytes/immunology , RNA, Viral/genetics , SARS-CoV-2/physiology , Adenosine/metabolism , Cluster Analysis , Computational Biology/methods , Disease Susceptibility/immunology , Gene Expression Profiling , Humans , Leukocytes/metabolism , RNA, Viral/metabolism , ROC Curve
3.
Front Immunol ; 12: 776933, 2021.
Article in English | MEDLINE | ID: covidwho-1581333

ABSTRACT

The efficacy of COVID-19 vaccines appears to depend in complex ways on the vaccine dosage and the interval between the prime and boost doses. Unexpectedly, lower dose prime and longer prime-boost intervals have yielded higher efficacies in clinical trials. To elucidate the origins of these effects, we developed a stochastic simulation model of the germinal center (GC) reaction and predicted the antibody responses elicited by different vaccination protocols. The simulations predicted that a lower dose prime could increase the selection stringency in GCs due to reduced antigen availability, resulting in the selection of GC B cells with higher affinities for the target antigen. The boost could relax this selection stringency and allow the expansion of the higher affinity GC B cells selected, improving the overall response. With a longer dosing interval, the decay in the antigen with time following the prime could further increase the selection stringency, amplifying this effect. The effect remained in our simulations even when new GCs following the boost had to be seeded by memory B cells formed following the prime. These predictions offer a plausible explanation of the observed paradoxical effects of dosage and dosing interval on vaccine efficacy. Tuning the selection stringency in the GCs using prime-boost dosages and dosing intervals as handles may help improve vaccine efficacies.


Subject(s)
B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Clonal Selection, Antigen-Mediated/immunology , Germinal Center/immunology , Host-Pathogen Interactions/immunology , SARS-CoV-2/immunology , Antigens/immunology , B-Lymphocytes/metabolism , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Dose-Response Relationship, Immunologic , Germinal Center/metabolism , Humans , Immunization, Secondary , Models, Theoretical , Vaccination
4.
Front Immunol ; 12: 780594, 2021.
Article in English | MEDLINE | ID: covidwho-1581329

ABSTRACT

Background: Dialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare. Methods: In this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients. Results: Four weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10-05). Conclusions: Peritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.


Subject(s)
/immunology , Antibody Formation/immunology , COVID-19/immunology , Host-Pathogen Interactions/immunology , Immunocompromised Host , Peritoneal Dialysis , SARS-CoV-2/immunology , /administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/prevention & control , Cohort Studies , Comorbidity , Female , Humans , Immunogenicity, Vaccine , Male , Middle Aged , Retrospective Studies , Vaccination
5.
Front Immunol ; 12: 794642, 2021.
Article in English | MEDLINE | ID: covidwho-1581317

ABSTRACT

Background: The relationships of the coronavirus disease 2019 (COVID-19) vaccination with reactogenicity and the humoral immune response are important to study. The current study aimed to assess the reactogenicity and immunogenicity of the Pfizer and AstraZeneca COVID-19 vaccines among adults in Madinah, Saudi Arabia. Methods: A cross-sectional study, including 365 randomly selected adult Pfizer or AstraZeneca vaccine recipients who received a homologous prime-boost vaccination between February 1st and June 30th, 2021. Data of height and weight were collected to assess the weight status of percipients. An evaluation of seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies was assessed using enzyme-linked immunosorbent assay (ELISA). Results: Among the participants, 69% (n = 250) reported at least one vaccine-related symptom. Pain at the injection site was the most frequently reported vaccine-related symptom. The mean total score for vaccine-related symptoms was significantly higher among participants who received the AstraZeneca vaccine, women, and participants with no previous COVID-19 infection (p < 0.05). Spike-specific IgG antibodies were detected in 98.9% of participants after the receipt of two vaccine doses, including 99.5% of Pfizer vaccine recipients and 98.3% of AstraZeneca vaccine recipients. Significantly, higher proportions of participants in the <35-year age group developed a humoral immune response after the first vaccine dose compared with the participants in other age groups. Conclusion: Participants who received the Pfizer COVID-19 vaccine reported fewer vaccine-related complications compared with those who received the AstraZeneca COVID-19 vaccine, but no serious side effects were reported in response to either vaccine. Health status and age were factors that may influence COVID-19 vaccine effectiveness for the generation of antibodies against the SARS-CoV-2 spike protein.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/standards , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adult , Aged , Antibody Formation/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Host-Pathogen Interactions/immunology , Humans , Immunization, Secondary , Immunoglobulin G , Male , Middle Aged , Online Systems , Public Health Surveillance , Surveys and Questionnaires
6.
Signal Transduct Target Ther ; 6(1): 420, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585885

ABSTRACT

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Host-Pathogen Interactions/genetics , Receptors, Virus/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Gene Expression , HEK293 Cells , Host-Pathogen Interactions/immunology , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Protein Binding , Protein Domains , Receptors, Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Virus Replication
7.
Front Immunol ; 12: 778913, 2021.
Article in English | MEDLINE | ID: covidwho-1574246

ABSTRACT

The current global pandemic of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causing COVID-19, has infected millions of people and continues to pose a threat to many more. Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the Renin-Angiotensin System (RAS) expressed on the surface of the lung, heart, kidney, neurons, and endothelial cells, which mediates SARS-CoV-2 entry into the host cells. The cytokine storms of COVID-19 arise from the large recruitment of immune cells because of the dis-synchronized hyperactive immune system, lead to many abnormalities including hyper-inflammation, endotheliopathy, and hypercoagulability that produce multi-organ dysfunction and increased the risk of arterial and venous thrombosis resulting in more severe illness and mortality. We discuss the aberrated interconnectedness and forthcoming crosstalks between immunity, the endothelium, and coagulation, as well as how sex disparities affect the severity and outcome of COVID-19 and harm men especially. Further, our conceptual framework may help to explain why persistent symptoms, such as reduced physical fitness and fatigue during long COVID, may be rooted in the clotting system.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2 , Biomarkers , Blood Coagulation , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , COVID-19/complications , COVID-19/diagnosis , Cytokines/metabolism , Disease Susceptibility , Endothelium/metabolism , Female , Host-Pathogen Interactions/immunology , Humans , Inflammation Mediators , Male , Renin-Angiotensin System , Severity of Illness Index , Sex Factors
8.
Antioxid Redox Signal ; 35(16): 1376-1392, 2021 12.
Article in English | MEDLINE | ID: covidwho-1510864

ABSTRACT

Significance: It is estimated that close to 50 million cases of sepsis result in over 11 million annual fatalities worldwide. The pathognomonic feature of sepsis is a dysregulated inflammatory response arising from viral, bacterial, or fungal infections. Immune recognition of pathogen-associated molecular patterns is a hallmark of the host immune defense to combat microbes and to prevent the progression to sepsis. Mitochondrial antiviral signaling protein (MAVS) is a ubiquitous adaptor protein located at the outer mitochondrial membrane, which is activated by the cytosolic pattern recognition receptors, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5), following binding of viral RNA agonists. Recent Advances: Substantial progress has been made in deciphering the activation of the MAVS pathway with its interacting proteins, downstream signaling events (interferon [IFN] regulatory factors, nuclear factor kappa B), and context-dependent type I/III IFN response. Critical Issues: In the evolutionary race between pathogens and the host, viruses have developed immune evasion strategies for cleavage, degradation, or blockade of proteins in the MAVS pathway. For example, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M protein and ORF9b protein antagonize MAVS signaling and a protective type I IFN response. Future Directions: The role of MAVS as a sensor for nonviral pathogens, host cell injury, and metabolic perturbations awaits better characterization in the future. New technical advances in multidimensional single-cell analysis and single-molecule methods will accelerate the rate of new discoveries. The ultimate goal is to manipulate MAVS activities in the form of immune-modulatory therapies to combat infections and sepsis. Antioxid. Redox Signal. 35, 1376-1392.


Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Sepsis/immunology , Signal Transduction/immunology , Virus Diseases/immunology , Animals , Host-Pathogen Interactions/immunology , Humans , Immune Evasion/immunology , Sepsis/virology
9.
Front Immunol ; 12: 732913, 2021.
Article in English | MEDLINE | ID: covidwho-1504188

ABSTRACT

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the viral infection that develops into a severe course of COVID-19. Moreover, sequela studies of individuals 6 months after having COVID-19 show a higher risk of metabolic comorbidities including obesity, diabetes, and kidney disease. These collectively implicate an inter-systemic dimension to understanding the association between obesity and COVID-19 and suggest an interdisciplinary intervention for relief of obesity-COVID-19 complications beyond the phase of acute infection.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Obesity/immunology , Obesity/metabolism , COVID-19/complications , Disease Progression , Host-Pathogen Interactions/immunology , Humans , Immunity , Metabolic Diseases/immunology , Metabolic Diseases/metabolism , Obesity/complications , Prognosis , SARS-CoV-2/pathogenicity , Severity of Illness Index
10.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166295, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1491726

ABSTRACT

Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1ß were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor ß (Erß), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.


Subject(s)
COVID-19/metabolism , COVID-19/virology , Host-Pathogen Interactions , Ovary/metabolism , Reproductive Techniques, Assisted , SARS-CoV-2 , Adult , Antibodies, Viral/immunology , Biomarkers , COVID-19/immunology , Cells, Cultured , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Fertility , Follicular Fluid/metabolism , Granulosa Cells/metabolism , Host-Pathogen Interactions/immunology , Humans , Immunoglobulin G/immunology , Oocytes/metabolism , Young Adult
11.
Genome Biol Evol ; 13(11)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1483441

ABSTRACT

Adenosine Deaminases that Act on RNA (ADARs) are RNA editing enzymes that play a dynamic and nuanced role in regulating transcriptome and proteome diversity. This editing can be highly selective, affecting a specific site within a transcript, or nonselective, resulting in hyperediting. ADAR editing is important for regulating neural functions and autoimmunity, and has a key role in the innate immune response to viral infections, where editing can have a range of pro- or antiviral effects and can contribute to viral evolution. Here we examine the role of ADAR editing across a broad range of viral groups. We propose that the effect of ADAR editing on viral replication, whether pro- or antiviral, is better viewed as an axis rather than a binary, and that the specific position of a given virus on this axis is highly dependent on virus- and host-specific factors, and can change over the course of infection. However, more research needs to be devoted to understanding these dynamic factors and how they affect virus-ADAR interactions and viral evolution. Another area that warrants significant attention is the effect of virus-ADAR interactions on host-ADAR interactions, particularly in light of the crucial role of ADAR in regulating neural functions. Answering these questions will be essential to developing our understanding of the relationship between ADAR editing and viral infection. In turn, this will further our understanding of the effects of viruses such as SARS-CoV-2, as well as many others, and thereby influence our approach to treating these deadly diseases.


Subject(s)
Adenosine Deaminase/metabolism , RNA Editing , RNA Viruses/genetics , Adenosine Deaminase/genetics , Animals , Evolution, Molecular , Host-Pathogen Interactions/immunology , Humans , Immunity , RNA Viruses/classification , RNA Viruses/physiology , RNA, Viral/genetics , RNA, Viral/metabolism , Virus Replication/genetics
12.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166285, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1460712

ABSTRACT

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.


Subject(s)
COVID-19/etiology , COVID-19/transmission , Mycoplasma Infections/etiology , Mycoplasma Infections/transmission , Pregnancy Complications, Infectious , Zika Virus Infection/etiology , Zika Virus Infection/transmission , Biomarkers , Breast Feeding/adverse effects , Disease Susceptibility , Female , Host-Pathogen Interactions/immunology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Maternal-Fetal Exchange , Mycoplasma , Placenta/immunology , Placenta/metabolism , Placenta/microbiology , Placenta/virology , Pregnancy , SARS-CoV-2 , Zika Virus
13.
Viruses ; 13(9)2021 09 21.
Article in English | MEDLINE | ID: covidwho-1430982

ABSTRACT

Evidence is emerging that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect various organs of the body, including cardiomyocytes and cardiac endothelial cells in the heart. This review focuses on the effects of SARS-CoV-2 in the heart after direct infection that can lead to myocarditis and an outline of potential treatment options. The main points are: (1) Viral entry: SARS-CoV-2 uses specific receptors and proteases for docking and priming in cardiac cells. Thus, different receptors or protease inhibitors might be effective in SARS-CoV-2-infected cardiac cells. (2) Viral replication: SARS-CoV-2 uses RNA-dependent RNA polymerase for replication. Drugs acting against ssRNA(+) viral replication for cardiac cells can be effective. (3) Autophagy and double-membrane vesicles: SARS-CoV-2 manipulates autophagy to inhibit viral clearance and promote SARS-CoV-2 replication by creating double-membrane vesicles as replication sites. (4) Immune response: Host immune response is manipulated to evade host cell attacks against SARS-CoV-2 and increased inflammation by dysregulating immune cells. Efficiency of immunosuppressive therapy must be elucidated. (5) Programmed cell death: SARS-CoV-2 inhibits programmed cell death in early stages and induces apoptosis, necroptosis, and pyroptosis in later stages. (6) Energy metabolism: SARS-CoV-2 infection leads to disturbed energy metabolism that in turn leads to a decrease in ATP production and ROS production. (7) Viroporins: SARS-CoV-2 creates viroporins that lead to an imbalance of ion homeostasis. This causes apoptosis, altered action potential, and arrhythmia.


Subject(s)
COVID-19/complications , COVID-19/virology , Heart Diseases/etiology , SARS-CoV-2/physiology , Apoptosis , Autophagy , Disease Management , Disease Susceptibility , Endothelial Cells/ultrastructure , Endothelial Cells/virology , Heart Diseases/diagnosis , Heart Diseases/therapy , Host-Pathogen Interactions/immunology , Humans , Myocarditis/diagnosis , Myocarditis/etiology , Myocarditis/therapy , Viroporin Proteins , Virus Replication
14.
Viruses ; 13(9)2021 09 20.
Article in English | MEDLINE | ID: covidwho-1430981

ABSTRACT

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.


Subject(s)
COVID-19/immunology , COVID-19/prevention & control , Host-Pathogen Interactions/immunology , Immunocompromised Host , Organ Transplantation , SARS-CoV-2/immunology , Transplant Recipients , COVID-19/complications , COVID-19/virology , COVID-19 Vaccines/immunology , Combined Modality Therapy , Cytokine Release Syndrome/etiology , Disease Management , Disease Susceptibility , Humans , Immunity, Cellular , Immunity, Humoral , Organ Transplantation/adverse effects , Vaccination , Virus Shedding/immunology
15.
Viruses ; 13(9)2021 09 18.
Article in English | MEDLINE | ID: covidwho-1430977

ABSTRACT

The causal connection between serum biomarkers and COVID-19 severity or pathogenicity in children is unclear. The aim of this study was to describe clinical and immunological features of children affected by COVID-19. The secondary aim was to evaluate whether these cytokines could predict severity of COVID-19. All children (aged 0-18) admitted to the Pediatric Emergency Department and tested with nasopharyngeal swab for SARS-CoV-2 were recruited and assigned to three groups: COVID-19, other infections, control group. Clinical and laboratory data of these patients, including circulating cytokine levels, were analyzed in three groups. Fever was the most frequent symptom in COVID-19 (67.3%). Neutropenia was found in the COVID-19 group (p < 0.05); no difference was observed for lymphocyte counts in the three groups. Higher levels of IL-6 and TNF-alpha were found in the COVID-19 group compared to other infections and control groups (p = 0.014 and p = 0.001, respectively). Whereas, in the COVID-19 group, no difference was observed as for the same cytokines among sub-groups of different disease severity (p = 0.7 and p = 0.8). Serum levels of IL-6 and TNF-alpha were higher in COVID-19 children than in children with other infectious diseases, but those levels did not correlate with disease severity. Clinical studies in a large pediatric population are necessary to better define the role of the immune-mediated response in SARS-CoV-2 infections in children.


Subject(s)
COVID-19/metabolism , COVID-19/virology , Cytokines/biosynthesis , Host-Pathogen Interactions , SARS-CoV-2/physiology , Age Factors , Biomarkers , COVID-19/epidemiology , COVID-19/immunology , Child , Child, Preschool , Comorbidity , Female , Host-Pathogen Interactions/immunology , Humans , Male , Severity of Illness Index
16.
Viruses ; 13(9)2021 09 15.
Article in English | MEDLINE | ID: covidwho-1411083

ABSTRACT

Type I Interferons (IFN-I) are a family of potent antiviral cytokines that act through the direct restriction of viral replication and by enhancing antiviral immunity. However, these powerful cytokines are a caged lion, as excessive and sustained IFN-I production can drive immunopathology during infection, and aberrant IFN-I production is a feature of several types of autoimmunity. As specialized producers of IFN-I plasmacytoid (p), dendritic cells (DCs) can secrete superb quantities and a wide breadth of IFN-I isoforms immediately after infection or stimulation, and are the focus of this review. Notably, a few days after viral infection pDCs tune down their capacity for IFN-I production, producing less cytokines in response to both the ongoing infection and unrelated secondary stimulations. This process, hereby referred to as "pDC exhaustion", favors viral persistence and associates with reduced innate responses and increased susceptibility to secondary opportunistic infections. On the other hand, pDC exhaustion may be a compromise to avoid IFN-I driven immunopathology. In this review we reflect on the mechanisms that initially induce IFN-I and subsequently silence their production by pDCs during a viral infection. While these processes have been long studied across numerous viral infection models, the 2019 coronavirus disease (COVID-19) pandemic has brought their discussion back to the fore, and so we also discuss emerging results related to pDC-IFN-I production in the context of COVID-19.


Subject(s)
COVID-19/metabolism , COVID-19/virology , Host-Pathogen Interactions , Interferon Type I/biosynthesis , SARS-CoV-2/physiology , Biomarkers , COVID-19/immunology , Cytokines/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/immunology , Immunomodulation , Toll-Like Receptors/metabolism
17.
Theranostics ; 11(18): 9133-9161, 2021.
Article in English | MEDLINE | ID: covidwho-1410987

ABSTRACT

During an epidemic or pandemic, the primary task is to rapidly develop precise diagnostic approaches and effective therapeutics. Oligonucleotide aptamer-based pathogen detection assays and control therapeutics are promising, as aptamers that specifically recognize and block pathogens can be quickly developed and produced through simple chemical synthesis. This work reviews common aptamer-based diagnostic techniques for communicable diseases and summarizes currently available aptamers that target various pathogens, including the SARS-CoV-2 virus. Moreover, this review discusses how oligonucleotide aptamers might be leveraged to control pathogen propagation and improve host immune system responses. This review offers a comprehensive data source to the further develop aptamer-based diagnostics and therapeutics specific for infectious diseases.


Subject(s)
Aptamers, Nucleotide , Bacteria/genetics , Communicable Diseases/diagnosis , Molecular Diagnostic Techniques/methods , Viruses/genetics , Aptamers, Nucleotide/pharmacology , Biosensing Techniques , COVID-19 Testing/methods , Communicable Disease Control , Communicable Diseases/microbiology , Communicable Diseases/virology , Enzyme-Linked Immunosorbent Assay/methods , Host-Pathogen Interactions/immunology , Humans , SELEX Aptamer Technique , Virus Internalization
18.
Curr Opin Allergy Clin Immunol ; 21(6): 515-524, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1398151

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV2)/COVID-19 pandemic has reminded us of the fundamental and nonredundant role played by the innate and adaptive immune systems in host defense against emerging pathogens. The study of rare 'experiments of nature' in the setting of inborn errors of immunity (IEI) caused by monogenic germline variants has revealed key insights into the molecular and cellular requirements for immune-mediated protection against infectious diseases. This review will provide an overview of the discoveries obtained from investigating severe COVID-19 in patients with defined IEI or otherwise healthy individuals. RECENT FINDINGS: Genetic, serological and cohort studies have provided key findings regarding host defense against SARS-CoV2 infection, and mechanisms of disease pathogenesis. Remarkably, the risk factors, severity of disease, and case fatality rate following SARS-CoV2 infection in patients with IEI were not too dissimilar to that observed for the general population. However, the type I interferon (IFN) signaling pathway - activated in innate immune cells in response to viral sensing - is critical for anti-SARS-CoV2 immunity. Indeed, genetic variants or autoAbs affecting type I IFN function account for up to 20% of all cases of life-threatening COVID-19. SUMMARY: The analysis of rare cases of severe COVID-19, coupled with assessing the impact of SARS-CoV2 infection in individuals with previously diagnosed IEI, has revealed fundamental aspects of human immunology, disease pathogenesis and immunopathology in the context of exposure to and infection with a novel pathogen. These findings can be leveraged to improve therapies for treating for emerging and established infectious diseases.


Subject(s)
COVID-19/immunology , Host-Pathogen Interactions/genetics , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Host-Pathogen Interactions/immunology , Humans , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/genetics , Risk Factors , Severity of Illness Index
20.
Viruses ; 13(9)2021 09 02.
Article in English | MEDLINE | ID: covidwho-1390789

ABSTRACT

SARS-CoV-2 uses ACE2 and TMPRSS2 to gain entry into the cell. However, recent studies have shown that SARS-CoV-2 may use additional host factors that are required for the viral lifecycle. Here we used publicly available datasets, CoV-associated genes, and machine learning algorithms to explore the SARS-CoV-2 interaction landscape in different tissues. We found that in general a small fraction of cells express ACE2 in the different tissues, including nasal, bronchi, and lungs. We show that a small fraction of immune cells (including T cells, macrophages, dendritic cells) found in tissues also express ACE2. We show that healthy circulating immune cells do not express ACE2 and TMPRSS2. However, a small fraction of circulating immune cells (including dendritic cells, monocytes, T cells) in the PBMC of COVID-19 patients express ACE2 and TMPRSS2. Additionally, we found that a large spectrum of cells (in tissues and circulation) in both healthy and COVID-19-positive patients were significantly enriched for SARS-CoV-2 factors, such as those associated with RHOA and RAB GTPases, mRNA translation proteins, COPI- and COPII-mediated transport, and integrins. Thus, we propose that further research is needed to explore if SARS-CoV-2 can directly infect tissue and circulating immune cells to better understand the virus' mechanism of action.


Subject(s)
COVID-19/etiology , Disease Susceptibility , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , SARS-CoV-2/physiology , Virus Internalization , COVID-19/blood , Dendritic Cells/immunology , Dendritic Cells/metabolism , Gene Expression Profiling , Gene Expression Regulation , High-Throughput Nucleotide Sequencing , Humans , Immune System/immunology , Immune System/metabolism , Immunity, Innate , Macrophages/immunology , Macrophages/metabolism , Single-Cell Analysis
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