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1.
Biosens Bioelectron ; 209: 114222, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1778011

ABSTRACT

The 21st century has already brought us a plethora of new threats related to viruses that emerge in humans after zoonotic transmission or drastically change their geographic distribution or prevalence. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first spotted at the end of 2019 to rapidly spread in southwest Asia and later cause a global pandemic, which paralyzes the world since then. We have designed novel immunosensors targeting conserved protein sequences of the N protein of SARS-CoV-2 based on lab-produced and purified anti-SARS-CoV-2 nucleocapsid antibodies that are densely grafted onto various surfaces (diamond/gold/glassy carbon). Titration of antibodies shows very strong reactions up to 1:72 900 dilution. Next, we showed the mechanism of interactions of our immunoassay with nucleocapsid N protein revealing molecular recognition by impedimetric measurements supported by hybrid modeling results with both density functional theory and molecular dynamics methods. Biosensors allowed for a fast (in less than 10 min) detection of SARS-CoV-2 virus with a limit of detection from 0.227 ng/ml through 0.334 ng/ml to 0.362 ng/ml for glassy carbon, boron-doped diamond, and gold surfaces, respectively. For all tested surfaces, we obtained a wide linear range of concentrations from 4.4 ng/ml to 4.4 pg/ml. Furthermore, our sensor leads to a highly specific response to SARS-CoV-2 clinical samples versus other upper respiratory tract viruses such as influenza, respiratory syncytial virus, or Epstein-Barr virus. All clinical samples were tested simultaneously on biosensors and real-time polymerase chain reactions.


Subject(s)
Biosensing Techniques , COVID-19 , Epstein-Barr Virus Infections , Antibodies, Viral , Biosensing Techniques/methods , Boron , COVID-19/diagnosis , Carbon , Diamond , Gold , Herpesvirus 4, Human , Humans , Immunoassay/methods , Nucleocapsid , Nucleocapsid Proteins , SARS-CoV-2
2.
J Integr Neurosci ; 21(2): 73, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1776815

ABSTRACT

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Individuals affected by the disease gradually lose their capacity for abstract thinking, understanding, communication and memory. As populations age, declining cognitive abilities will represent an increasing global health concern. While AD was first described over a century ago, its pathogenesis remains to be fully elucidated. It is believed that cognitive decline in AD is caused by a progressive loss of neurons and synapses that lead to reduced neural plasticity. AD is a multifactorial disease affected by genetic and environmental factors. The molecular hallmarks of AD include formation of extracellular ß amyloid (Aß) aggregates, neurofibrillary tangles of hyperphosphorylated tau protein, excessive oxidative damage, an imbalance of biothiols, dysregulated methylation, and a disproportionate inflammatory response. Recent reports have shown that viruses (e.g., Herpes simplex type 1, 2, 6A/B; human cytomegalovirus, Epstein-Barr virus, hepatitis C virus, influenza virus, and severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), bacteria (e.g., Treponema pallidum, Borrelia burgdorferi, Chlamydia pneumoniae, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcmitans, Eikenella corrodens, Treponema denticola, and Helicobacter pylori), as well as eukaryotic unicellular parasites (e.g., Toxoplasma gondii) may factor into cognitive decline within the context of AD. Microorganisms may trigger pathological changes in the brain that resemble and/or induce accumulation of Aß peptides and promote tau hyperphosphorylation. Further, the mere presence of infectious agents is suspected to induce both local and systemic inflammatory responses promoting cellular damage and neuronal loss. Here we review the influence of infectious agents on the development of AD to inspire new research in dementia based on these pathogens.


Subject(s)
Alzheimer Disease , COVID-19 , Epstein-Barr Virus Infections , Alzheimer Disease/metabolism , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Humans , SARS-CoV-2
3.
Virol J ; 19(1): 50, 2022 03 19.
Article in English | MEDLINE | ID: covidwho-1745445

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered the worldwide coronavirus disease 2019 (COVID-19) pandemic. Serological assays for the detection of SARS-CoV-2 infections are important to understand the immune response in patients and to obtain epidemiological data about the number of infected people, especially to identify asymptomatic persons not aware of a past infection. METHODS: We recombinantly produced SARS-CoV-2 nucleocapsid (N)-protein in Escherichia coli. We used the purified protein to develop an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of SARS-CoV-2 specific antibodies. This ELISA method was optimized and validated with serum samples collected from 113 patients with RT-PCR-confirmed SARS-CoV-2 infections including hospitalized COVID-19 patients and 1500 control sera mostly collected before 2015 with different clinical background. RESULTS: The optimized N-protein-ELISA provided a sensitivity of 89.7% (n = 68) for samples collected from patients with confirmed SARS-CoV-2 infections and mild to severe symptoms more than 14 days after symptom onset or a positive PCR test. The antibody levels remained low for serum samples collected in the first six days (n = 23) and increased in the second week (n = 22) post symptom onset or PCR confirmation. At this early phase, the ELISA provided a sensitivity of 39.1% and 86.4%, respectively, reflecting the time of an IgG immune response against pathogens. The assay specificity was 99.3% (n = 1500; 95% CI 0.995-0.999). Serum samples from persons with confirmed antibody titers against human immunodeficiency viruses 1/2, parvovirus B19, hepatitis A/B virus, cytomegalovirus, Epstein Barr virus, and herpes simplex virus were tested negative. CONCLUSIONS: We conclude that the N-protein-based ELISA developed here is well suited for the sensitive and specific serological detection of SARS-CoV-2 specific IgG antibodies in human serum for symptomatic infections. It may also prove useful to identify previous SARS-CoV-2 infections in vaccinated people, as all currently approved vaccines rely on the SARS-CoV-2 spike (S-) protein.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Herpesvirus 4, Human , Humans , Nucleocapsid Proteins , SARS-CoV-2
4.
Antimicrob Agents Chemother ; 66(3): e0239521, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1741569

ABSTRACT

Recently, remdesivir and molnupiravir were approved for treating COVID-19 caused by SARS-CoV-2 infection. However, little is known about the impact of these drugs on other viruses preexisted in COVID-19 patients. Here we report that remdesivir but not molnupiravir induced lytic reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), two major oncogenic herpesviruses. Remdesivir induced mature virion production from latently infected cells. Mechanistic studies showed that remdesivir induced KSHV and EBV reactivation by regulating several intracellular signaling pathways.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Herpesvirus 8, Human , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Herpesvirus 4, Human/physiology , Humans , SARS-CoV-2 , Signal Transduction , Virus Activation
5.
Immun Inflamm Dis ; 10(4): e597, 2022 04.
Article in English | MEDLINE | ID: covidwho-1739166

ABSTRACT

BACKGROUND: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain. METHODS: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. RESULTS: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients. CONCLUSION: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , COVID-19/drug therapy , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/drug therapy , Female , Ganciclovir/therapeutic use , Herpesvirus 4, Human/physiology , Humans , Retrospective Studies , SARS-CoV-2
6.
J Investig Med High Impact Case Rep ; 10: 23247096221079192, 2022.
Article in English | MEDLINE | ID: covidwho-1714634

ABSTRACT

A 35-year-old female with no medical history presented with fever. Laboratory work was normal except for elevated liver function test (LFT): alkaline phosphatase (AP) (296), aspartate transaminase (AST) (343), alanine transaminase (ALT) (378), and international normalized ratio (INR) (1.23). Ultrasound liver was normal. Infectious workup was negative for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes simplex virus (HSV), and COVID-19. Similarly, autoimmune hepatitis, Wilson, and alpha-1 antitrypsin workup were negative. She reported taking Yogi-Kanthika (ayurvedic-proprietary medicine) on/off for seasonal sore throat, yet RUCAM-score was 2 (unlikely a drug induced injury). Respiratory-viral-panel came positive for adenovirus. With supportive treatment, symptoms and LFT trended down, thus, liver biopsy decision was deferred. We believe this is the first reported case of adenovirus hepatitis in an immunocompetent adult. Hence, we suggest that clinicians should consider a refined differential diagnosis for elevated LFT (that includes adenovirus).


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Hepatitis, Viral, Human , Adenoviridae , Adult , Epstein-Barr Virus Infections/diagnosis , Female , Hepatitis, Viral, Human/diagnosis , Herpesvirus 4, Human , Humans , SARS-CoV-2
7.
Einstein (Sao Paulo) ; 20: eRC6541, 2022.
Article in English | MEDLINE | ID: covidwho-1687843

ABSTRACT

Acute vulvar ulcer (Lipschütz's ulcer) is a rare lesion with local hyperimmunoreactivity triggered by infection, which is characterized by acute, painful, and necrotic ulcerations. This condition is usually found in non-sexually active adolescents, and it resolves spontaneously. We report a case of a 35-year-old woman who was diagnosed with COVID-19 who did not have severe symptoms, but had high levels of D-dimer for 9 days. The COVID-19 diagnosis was followed by the appearance of an acute, necrotic, extremely painful vulvar ulcer, although symptoms caused by COVID-19 had improved. We emphasize the importance of the differential diagnosis to exclude diseases such as Behçet's syndrome, Sexually Transmitted Infections, as well as the presence of viruses that generally trigger Lipschütz's ulcer, such as Epstein-Barr virus and cytomegalovirus. No treatment is usually necessary, however, in the present report due to the pain experienced by the patient, we successfully used oral prednisone.


Subject(s)
Behcet Syndrome , COVID-19 , Epstein-Barr Virus Infections , Adolescent , Adult , Behcet Syndrome/complications , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , COVID-19 Testing , Female , Genitalia , Herpesvirus 4, Human , Humans , SARS-CoV-2 , Ulcer/drug therapy
8.
Pediatr Dermatol ; 39(1): 77-83, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1607511

ABSTRACT

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, an increasing number of chilblain-like lesions (ChLL) have been increasingly reported worldwide. To date, the causal link between ChLL and SARS-CoV-2 infection has not been unequivocally established. METHODS: In this case series, we present demographic, clinical, laboratory, and histopathological information regarding 27 young patients with a clinical diagnosis of ChLL who referred to the Dermatology Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, from 1 April 2020 to 1 June 2020. RESULTS: The mean age was 14.2 years, and 21 patients (78%) experienced mild systemic symptoms a median of 28 days before the onset of cutaneous lesions. ChLL mostly involved the feet (20 patients - 74%). Among acral lesions, we identified three different clinical patterns: (i) chilblains in 20 patients (74%); (ii) fixed erythematous macules in 4 children (15%); (iii) erythrocyanosis in 3 female patients (11%). Blood examinations and viral serologies, including parvovirus B19, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and coxsackievirus were normal in all. Three patients (11%) underwent nasopharyngeal swab for RT-PCR for SARS-CoV-2 showing only 1 positive. Histopathological examinations of 7 skin biopsies confirmed the clinical diagnosis of chilblains; vessel thrombi were observed only in 1 case. Our findings failed to demonstrate the direct presence of SARS-CoV-2 RNA in skin biopsies, both with real-time polymerase chain reaction (RT-PCR) and RNAscope in situ hybridization (ISH). LIMITATIONS: Limited number of cases, unavailability of laboratory confirmation of COVID-19 in all patients, potential methodological weakness, and latency of skin biopsies in comparison to cutaneous lesions onset. CONCLUSIONS: These observations may support the hypothesis of an inflammatory pathogenesis rather than the presence of peripheral viral particles. Although, we could not exclude an early phase of viral endothelial damage followed by an IFN-I or complement-mediated inflammatory phase. Further observations on a large number of patients are needed to confirm this hypothesis.


Subject(s)
COVID-19 , Chilblains , Epstein-Barr Virus Infections , Adolescent , Chilblains/diagnosis , Child , Female , Herpesvirus 4, Human , Humans , In Situ Hybridization , Laboratories , RNA, Viral , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
9.
J Transl Med ; 19(1): 496, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1561217

ABSTRACT

Pulmonary fibrosis is the end stage of a broad range of heterogeneous interstitial lung diseases and more than 200 factors contribute to it. In recent years, the relationship between virus infection and pulmonary fibrosis is getting more and more attention, especially after the outbreak of SARS-CoV-2 in 2019, however, the mechanisms underlying the virus-induced pulmonary fibrosis are not fully understood. Here, we review the relationship between pulmonary fibrosis and several viruses such as Human T-cell leukemia virus (HTLV), Human immunodeficiency virus (HIV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Murine γ-herpesvirus 68 (MHV-68), Influenza virus, Avian influenza virus, Middle East Respiratory Syndrome (MERS)-CoV, Severe acute respiratory syndrome (SARS)-CoV and SARS-CoV-2 as well as the mechanisms underlying the virus infection induced pulmonary fibrosis. This may shed new light on the potential targets for anti-fibrotic therapy to treat pulmonary fibrosis induced by viruses including SARS-CoV-2.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Pulmonary Fibrosis , SARS Virus , Virus Diseases , Animals , Herpesvirus 4, Human , Humans , Mice , Pulmonary Fibrosis/etiology , SARS-CoV-2
10.
Clin Infect Dis ; 73(11): e3970-e3973, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1559838

ABSTRACT

A woman with mild coronavirus disease 2019 developed cervical adenopathy, being diagnosed of Epstein-Barr virus infectious mononucleosis. We performed fine needle aspiration, and demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in lymph nodes even in mild disease along with a strong expansion of terminally differentiated effector memory CD4+ T cells, a cell population that is practically absent in lymph nodes.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , CD4-Positive T-Lymphocytes , Female , Herpesvirus 4, Human , Humans , Lymph Nodes , SARS-CoV-2
11.
BMJ Case Rep ; 14(11)2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1546473

ABSTRACT

Plasmablastic lymphoma (PBL) is an uncommon and aggressive type of mature B cell lymphoma rarely involving gastrointestinal (GI) tract. Here, we describe a case of PBL involving the colon in HIV/Epstein-Barr virus negative immunocompetent patient who presented with anaemia and weight loss but no significant GI symptoms. It emphasises that even in the absence of classical risk factors, one should consider possibility of this condition as this is potentially curable. Also, we would like to highlight the diagnostic and treatment challenges of such an aggressive lymphoma in a frail elderly patient with multiple comorbidities.


Subject(s)
Epstein-Barr Virus Infections , Lymphoma, B-Cell , Plasmablastic Lymphoma , Aged , Herpesvirus 4, Human , Humans , Plasmablastic Lymphoma/diagnosis , Plasmablastic Lymphoma/drug therapy , Risk Factors
12.
mBio ; 12(6): e0290721, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1518121

ABSTRACT

Oncogenic gammaherpesviruses express viral products during latent and lytic infection that block the innate immune response. Previously, we found that Kaposi's sarcoma herpesvirus (KSHV/human herpesvirus-8) viral microRNAs (miRNAs) downregulate cholesterol biogenesis, and we hypothesized that this prevents the production of 25-hydroxycholesterol (25HC), a cholesterol derivative. 25HC blocks KSHV de novo infection of primary endothelial cells at a postentry step and decreases viral gene expression of LANA (latency-associated nuclear antigen) and RTA. Herein we expanded on this observation by determining transcriptomic changes associated with 25HC treatment of primary endothelial cells using RNA sequencing (RNA-Seq). We found that 25HC treatment inhibited KSHV gene expression and induced interferon-stimulated genes (ISGs) and several inflammatory cytokines (interleukin 8 [IL-8], IL-1α). Some 25HC-induced genes were partially responsible for the broadly antiviral effect of 25HC against several viruses. Additionally, we found that 25HC inhibited infection of primary B cells by a related oncogenic virus, Epstein-Barr virus (EBV/human herpesvirus-4) by suppressing key viral genes such as LMP-1 and inducing apoptosis. RNA-Seq analysis revealed that IL-1 and IL-8 pathways were induced by 25HC in both primary endothelial cells and B cells. We also found that the gene encoding cholesterol 25-hydroxylase (CH25H), which converts cholesterol to 25HC, can be induced by type I interferon (IFN) in human B cell-enriched peripheral blood mononuclear cells (PBMCs). We propose a model wherein viral miRNAs target the cholesterol pathway to prevent 25HC production and subsequent induction of antiviral ISGs. Together, these results answer some important questions about a widely acting antiviral (25HC), with implications for multiple viral and bacterial infections. IMPORTANCE A cholesterol derivative, 25-hydroxycholesterol (25HC), has been demonstrated to inhibit infections from widely different bacteria and viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its mechanism of activity is still not fully understood. In this work, we look at gene expression changes in the host and virus after 25HC treatment to find clues about its antiviral activity. We likewise demonstrate that 25HC is also antiviral against EBV, a common cancer-causing virus. We compared our results with previous data from antiviral screening assays and found the same pathways resulting in antiviral activity. Together, these results bring us closer to understanding how a modified form of cholesterol works against several viruses.


Subject(s)
Cytokines/immunology , Epstein-Barr Virus Infections/immunology , Herpesvirus 4, Human/drug effects , Herpesvirus 8, Human/drug effects , Hydroxycholesterols/pharmacology , Hydroxycholesterols/therapeutic use , Inflammation/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/virology , Cells, Cultured , Cytokines/genetics , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Epstein-Barr Virus Infections/drug therapy , Gene Expression Regulation, Viral , Herpesvirus 4, Human/genetics , Herpesvirus 8, Human/genetics , Humans , Hydroxycholesterols/immunology , Sequence Analysis, RNA , Virus Latency , Virus Replication
13.
J Cosmet Dermatol ; 20(12): 3747-3750, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1501459

ABSTRACT

BACKGROUND: COVID-19 is associated with several cutaneous manifestations, including chilbain-like lesions, urticaria, erythema multiforme, and maculopapular lesions. Dermatoses may be directly linked to the viral infection or also represent a consequence of systemic therapies administrated for COVID-19. A potential role of SARS-CoV-2 in triggering the reactivation of other viruses, such as HHV-6, HHV-7 and Epstein-Barr virus has been hypothesized. OBJECTIVE: To better understand and hypothesize possible pathogenetic correlations of COVID-19 with other dermatological conditions. METHODS: We report the case of an 83-year-old woman hospitalized in a nursing home for several years. On November 2020, the patient had been diagnosed with SARS-CoV-2 infection, with repeated positive swabs until January 2021. After a month, new-onset asymptomatic cutaneous purplish macular lesions and violaceous patches occurred bilaterally on the feet. RESULTS: An incisional cutaneous biopsy and the histological examination of the plantar lesion revealed the diagnosis of Kaposi Sarcoma. CONCLUSION: We report a unique case of new-onset bilateral Kaposi's sarcoma following COVID-19, speculating on a possible role of SARS-CoV-2 in the reactivation of human herpes virus-8 (HHV-8) infection.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Sarcoma, Kaposi , Aged, 80 and over , Female , Herpesvirus 4, Human , Humans , SARS-CoV-2
14.
Arch Pediatr ; 28(7): 573-575, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1491712

ABSTRACT

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, cutaneous lesions are being described. Here, we report on a 13-year-old girl with SARS-CoV-2-associated Henoch-Schönlein purpura and Epstein-Barr virus (EBV) infection. She presented without any respiratory symptoms, only a purpuric skin rash, abdominal pain, low-grade fever, and pharyngitis. Virology tests by polymerase chain reaction (PCR) were positive for SARS-CoV-2 and EBV. The potential association of Henoch-Schönlein purpura and SARS-CoV-2 should be kept in mind in order to reduce the spread of the virus, particularly in children with few respiratory symptoms.


Subject(s)
COVID-19/diagnosis , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/isolation & purification , SARS-CoV-2/isolation & purification , Abdominal Pain/etiology , Adolescent , Epstein-Barr Virus Infections/complications , Exanthema/etiology , Female , Fever/etiology , Herpesvirus 4, Human/genetics , Humans , Pharyngitis/etiology , Polymerase Chain Reaction , SARS-CoV-2/genetics
15.
Biosens Bioelectron ; 195: 113672, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1439904

ABSTRACT

We present the first combination of a microfluidic polymerase chain reaction (PCR) with a gold nanoslit-based surface plasmon resonance (SPR) sensor for detecting the DNA sequence of latent membrane protein 1 (LMP1). The PCR microchannel was produced through a laser scribing technique, and the SPR nanoslit chip was manufactured via hot-embossing nanoimprinting lithography. Afterward, the LMP1 DNA probe was adsorbed onto the SPR chip of the integrated device through electrostatic interactions for further detection. The device can complete the analytical procedure in around 36 min, while the traditional machine requires 105 min to achieve similar signals under the same PCR thermal cycles. The calibration curve with serially diluted LMP1 DNA exhibited the accuracy (R2 > 0.99) and sensitivity (limit of detection: ∼10-11 g/mL) of the device. Moreover, extracted DNA from Epstein-Barr virus (EBV)-positive cells were directly detected through the integrated chip. In brief, this all-in-one chip can amplify gene fragments at the front-end and detect them at the back-end, decreasing the time required for the analysis without compromising accuracy or sensitivity. We believe this label-free, real-time, low-cost device has enormous potential for rapid detection of various viruses, such as EBV and COVID-19.


Subject(s)
Biosensing Techniques , COVID-19 , Epstein-Barr Virus Infections , Gold , Herpesvirus 4, Human/genetics , Humans , Microfluidics , Polymerase Chain Reaction , SARS-CoV-2 , Viral Matrix Proteins/genetics
16.
BMC Infect Dis ; 21(1): 955, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1414111

ABSTRACT

BACKGROUND: Our goal is to further elucidate the clinical condition and prognosis of patients with severe acute COVID-19 with EBV reactivation. METHOD: This is a retrospective single-center study of COVID-19 patients admitted to the intensive care unit of Wuhan No. 3 Hospital (January 31 to March 27, 2020). According to whether Epstein-Barr virus reactivation was detected, the patients were divided into an EBV group and a Non-EBV group. Baseline data were collected including epidemiological, larithmics, clinical and imaging characteristics, and laboratory examination data. RESULTS: Of the 128 patients with COVID-19, 17 (13.3%) were infected with Epstein-Barr virus reactivation. In the symptoms,the rate of tachypnoea in the EBV group was apparently higher than that in the Non-EBV group. In lab tests, the lymphocyte and albumin of EBV group decreased more significantly than Non-EBV group, and the D-dimer and serum calcium of EBV group was higher than Non-EBV group. Regarding the infection index, CRP of EBV group was apparently above the Non-EBV group, and no significant difference was found in procalcitonin of the two groups. The incidence of respiratory failure, ARDS, and hypoproteinaemia of EBV group had more incidence than Non-EBV group. The 28-day and 14-day mortality rates of EBV group was significantly higher than that of Non-EBV group. CONCLUSIONS: In the COVID-19 patients, patients with EBV reactivation had higher 28-day and 14-day mortality rates and received more immuno-supportive treatment than patients of Non-EBV group.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Critical Illness , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/epidemiology , Herpesvirus 4, Human , Humans , Retrospective Studies , SARS-CoV-2 , Virus Activation
17.
Virol J ; 18(1): 180, 2021 09 05.
Article in English | MEDLINE | ID: covidwho-1388778

ABSTRACT

BACKGROUND: Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2'-5'-oligoadenylate synthase-3, oas-3). CASE PRESENTATION: We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein-Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out. CONCLUSION: To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.


Subject(s)
COVID-19/genetics , COVID-19/virology , Hepatitis, Viral, Human/genetics , Hepatitis, Viral, Human/virology , Toll-Like Receptor 7/genetics , Antibodies, Viral/blood , COVID-19/immunology , Child, Preschool , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/virology , Feces/virology , Hepatitis, Viral, Human/immunology , Herpesvirus 4, Human/isolation & purification , Humans , Immunity, Innate , Influenza, Human , Male , Polymorphism, Single Nucleotide , SARS-CoV-2/isolation & purification
18.
J Investig Med High Impact Case Rep ; 9: 23247096211040626, 2021.
Article in English | MEDLINE | ID: covidwho-1371944

ABSTRACT

Epstein-Barr virus (EBV), a member of the herpes virus family, is a causative agent for infectious mononucleosis in young adults. It has an asymptomatic and subclinical distribution in about 90% to 95% of the world population based on seropositivity. EBV is associated with various lymphomas, nasopharyngeal carcinoma, and in immunocompromised states can give rise to aggressive lymphoproliferative disorders. Symptomatic patients mostly present with mild hepatitis, rash, oral symptoms, lymphadenopathy, and generalized malaise. Recently with the COVID-19 (coronavirus disease-2019) pandemic, hepatitis has been found to be related to acute EBV and cytomegalovirus reactivation versus acute infection in the absence of other major causes. We describe a case of EBV coinfection in a patient with resolving mild COVID-19 infection.


Subject(s)
COVID-19/complications , Coinfection , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , SARS-CoV-2 , Herpesvirus 4, Human/pathogenicity , Humans , Male , Middle Aged
19.
Immun Inflamm Dis ; 9(4): 1563-1572, 2021 12.
Article in English | MEDLINE | ID: covidwho-1366235

ABSTRACT

INTRODUCTION: Although most patients recover within several weeks after acute COVID-19, some of them develop long-lasting clinical symptoms. Renal transplant recipients have an increased mortality risk from COVID-19. We aimed to describe complications occurring after COVID-19 in this group of patients. METHODS: A prospective single-center cohort study was conducted at University Hospital Centre Zagreb. Patients with two negative reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 after COVID-19 were eligible for further follow-up at our outpatient clinic. They underwent detailed clinical and laboratory assessments. The primary outcome was the development of complications after COVID-19. RESULTS: Only 11.53% of renal transplant recipients who survived acute COVID-19 were symptomless and free from new-onset laboratory abnormalities during the median follow-up of 64 days (range: 50-76 days). Three patients died from sepsis after discharge from the hospital. In 47 patients (45.2%), clinical complications were present, while 74 patients (71.2%) had one or more laboratory abnormalities. The most common clinical complications included shortness of breath (19.2%), tiredness (11.5%), peripheral neuropathy (7.7%), self-reported cognitive impairments (5.7%), and dry cough (7.7%). Most common laboratory abnormalities included shortened activated partial thromboplastin time (50%), elevated D-dimers (36.5%), elevated fibrinogen (30.16%), and hypogammaglobulinemia (24%). Positive RT-PCR for cytomegalovirus (8.7%), Epstein-Barr virus (26%), or BK virus (16.3%). Multivariate analysis identified the history of diabetes mellitus and eGFR CKD-EPI as predictors for the development of post-COVID clinical complications. Six months after acute COVID-19, elevated D-dimers persisted with normalization of other laboratory parameters. Twenty-nine patients were hospitalized, mostly with several concomitant problems. However, initially reported clinical problems gradually improved in the majority of patients. CONCLUSION: Post-COVID-19 clinical and laboratory complications are frequent in the renal transplant population, in some of them associated with significant morbidity. All patients recovered from acute COVID-19 should undergo long-term monitoring for evaluation and treatment of complications.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Kidney Transplantation , Cohort Studies , Follow-Up Studies , Herpesvirus 4, Human , Humans , Kidney Transplantation/adverse effects , Prospective Studies , SARS-CoV-2
20.
Arch Pediatr ; 28(7): 573-575, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1358159

ABSTRACT

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, cutaneous lesions are being described. Here, we report on a 13-year-old girl with SARS-CoV-2-associated Henoch-Schönlein purpura and Epstein-Barr virus (EBV) infection. She presented without any respiratory symptoms, only a purpuric skin rash, abdominal pain, low-grade fever, and pharyngitis. Virology tests by polymerase chain reaction (PCR) were positive for SARS-CoV-2 and EBV. The potential association of Henoch-Schönlein purpura and SARS-CoV-2 should be kept in mind in order to reduce the spread of the virus, particularly in children with few respiratory symptoms.


Subject(s)
COVID-19/diagnosis , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/isolation & purification , SARS-CoV-2/isolation & purification , Abdominal Pain/etiology , Adolescent , Epstein-Barr Virus Infections/complications , Exanthema/etiology , Female , Fever/etiology , Herpesvirus 4, Human/genetics , Humans , Pharyngitis/etiology , Polymerase Chain Reaction , SARS-CoV-2/genetics
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