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1.
Curr Microbiol ; 80(1): 15, 2022 Dec 02.
Article in English | MEDLINE | ID: covidwho-2245017

ABSTRACT

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Compared to other types of self-limiting myelin disorders, MS compartmentalizes and maintains chronic inflammation in the CNS. Even though the exact cause of MS is unclear, it is assumed that genetic and environmental factors play an important role in susceptibility to this disease. The progression of MS is triggered by certain environmental factors, such as viral infections. The most important viruses that affect MS are Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), human endogenous retrovirus (HERV), cytomegalovirus (CMV), and varicella zoster virus (VZV). These viruses all have latent stages that allow them to escape immune detection and reactivate after exposure to various stimuli. Furthermore, their tropism for CNS and immune system cells explains their possible deleterious function in neuroinflammation. In this study, the effect of viral infections on MS disease focuses on the details of viruses that can change the risk of the disease. Paying attention to the most recent articles on the role of SARS-CoV-2 in MS disease, laboratory indicators show the interaction of the immune system with the virus. Also, strategies to prevent viruses that play a role in triggering MS are discussed, such as EBV, which is one of the most important.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Multiple Sclerosis , Virus Diseases , Humans , Multiple Sclerosis/etiology , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , SARS-CoV-2 , Virus Diseases/complications
2.
J Med Virol ; 95(2): e28572, 2023 02.
Article in English | MEDLINE | ID: covidwho-2244758

ABSTRACT

Messenger RNA (mRNA) vaccines against COVID-19 are the first authorized biological preparations developed using this platform. During the pandemic, their administration has been proven to be a life-saving intervention. Here, we review the main advantages of using mRNA vaccines, identify further technological challenges to be met during the development of the mRNA platform, and provide an update on the clinical progress on leading mRNA vaccine candidates against different viruses that include influenza viruses, human immunodeficiency virus 1, respiratory syncytial virus, Nipah virus, Zika virus, human cytomegalovirus, and Epstein-Barr virus. The prospects and challenges of manufacturing mRNA vaccines in low-income countries are also discussed. The ongoing interest and research in mRNA technology are likely to overcome some existing challenges for this technology (e.g., related to storage conditions and immunogenicity of some components of lipid nanoparticles) and enhance the portfolio of vaccines against diseases for which classical formulations are already authorized. It may also open novel pathways of protection against infections and their consequences for which no safe and efficient immunization methods are currently available.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Influenza Vaccines , Respiratory Syncytial Virus, Human , Viral Vaccines , Virus Diseases , Zika Virus Infection , Zika Virus , Humans , COVID-19 Vaccines , Herpesvirus 4, Human/genetics , Respiratory Syncytial Virus, Human/genetics , RNA, Messenger , Zika Virus/genetics
3.
Biomolecules ; 13(1)2022 12 20.
Article in English | MEDLINE | ID: covidwho-2237631

ABSTRACT

This study was conducted to investigate oropharyngeal microbiota alterations during the progression of coronavirus disease 2019 (COVID-19) by analyzing these alterations during the infection and clearance processes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diagnosis of COVID-19 was confirmed by using positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR). The alterations in abundance, diversity, and potential function of the oropharyngeal microbiome were identified using metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 47 patients with COVID-19 (within a week after diagnosis and within two months after recovery from COVID-19) and 40 healthy individuals. As a result, in the infection process of SARS-CoV-2, compared to the healthy individuals, the relative abundances of Prevotella, Aspergillus, and Epstein-Barr virus were elevated; the alpha diversity was decreased; the beta diversity was disordered; the relative abundance of Gram-negative bacteria was increased; and the relative abundance of Gram-positive bacteria was decreased. After the clearance of SARS-CoV-2, compared to the healthy individuals and patients with COVID-19, the above disordered alterations persisted in the patients who had recovered from COVID-19 and did not return to the normal level observed in the healthy individuals. Additionally, the expressions of several antibiotic resistance genes (especially multi-drug resistance, glycopeptide, and tetracycline) in the patients with COVID-19 were higher than those in the healthy individuals. After SARS-CoV-2 was cleared, the expressions of these genes in the patients who had recovered from COVID-19 were lower than those in the patients with COVID-19, and they were different from those in the healthy individuals. In conclusion, our findings provide evidence that potential secondary infections with oropharyngeal bacteria, fungi, and viruses in patients who have recovered from COVID-19 should not be ignored; this evidence also highlights the clinical significance of the oropharyngeal microbiome in the early prevention of potential secondary infections of COVID-19 and suggests that it is imperative to choose appropriate antibiotics for subsequent bacterial secondary infection in patients with COVID-19.


Subject(s)
COVID-19 , Coinfection , Epstein-Barr Virus Infections , Microbiota , Humans , SARS-CoV-2/genetics , Herpesvirus 4, Human , Microbiota/genetics , Bacteria
4.
Viruses ; 15(1)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2230924

ABSTRACT

Initial diagnosis of human T cell lymphotropic virus (HTLV) infections is mainly based by detecting antibodies in plasma or serum using laboratory-based methods. The aim of this study was to develop and evaluate a rapid screening test for HTLV-I antibodies. Our rapid screening test uses HTLV-I p24 antigen conjugated to gold nanoparticles and an anti-human IgG antibody immobilized to a nitrocellulose strip to detect human HTLV-I p24-specific IgG antibodies via immunochromatography. Performance of the rapid screening test for HTLV-I was conducted on a total of 118 serum specimens collected in Salvador, Bahia, the epicenter for HTLV-1 infection in Brazil. Using a Western blot test as the comparator, 55 serum specimens were HTLV-I positive, 5 were HTLV-I and HTLV-II positive, and 58 were negative. The sensitivity of the rapid screening test for HTLV-1 was 96.7% and the specificity was 100%. The rapid screening test did not show cross-reaction with serum specimens from individuals with potentially interfering infections including those caused by HTLV-II, HIV-I, HIV-II, hepatitis A virus, hepatitis B virus, hepatitis C virus, herpes simplex virus, Epstein-Barr virus, SARS-CoV-2, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Toxoplasma gondii, and Plasmodium falciparum. The rapid screening test also did not show cross-reaction with potentially interfering substances. Strategies for HTLV diagnosis in non- and high-endemic areas can be improved with low-cost, rapid screening tests.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , HTLV-I Infections , Human T-lymphotropic virus 1 , Metal Nanoparticles , Humans , HTLV-I Antibodies , Gold , Herpesvirus 4, Human , SARS-CoV-2 , HTLV-I Infections/diagnosis , Deltaretrovirus
5.
Viruses ; 15(2)2023 Jan 31.
Article in English | MEDLINE | ID: covidwho-2225677

ABSTRACT

A novel syndrome called long-haul COVID or long COVID is increasingly recognized in a significant percentage of individuals within a few months after infection with SARS-CoV-2. This disorder is characterized by a wide range of persisting, returning or even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine and systemic. Some overlapping symptomatologies exist between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Very much like with long ME/CFS, infections with herpes family viruses, immune dysregulation, and the persistence of inflammation have been reported as the most common pattern for the development of long COVID. This review describes several factors and determinants of long COVID that have been proposed, elaborating mainly on viral persistence, reactivation of latent viruses such as Epstein-Barr virus and human herpesvirus 6 which are also associated with the pathology of ME/CFS, viral superantigen activation of the immune system, disturbance in the gut microbiome, and multiple tissue damage and autoimmunity. Based on these factors, we propose diagnostic strategies such as the measurement of IgG and IgM antibodies against SARS-CoV-2, EBV, HHV-6, viral superantigens, gut microbiota, and biomarkers of autoimmunity to better understand and manage this multi-factorial disorder that continues to affect millions of people in the world.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Fatigue Syndrome, Chronic , Herpesvirus 6, Human , Humans , Post-Acute COVID-19 Syndrome , Herpesvirus 4, Human , Autoimmunity , Epstein-Barr Virus Infections/complications , SARS-CoV-2 , Inflammation
6.
Int J Clin Pract ; 2023: 1068000, 2023.
Article in English | MEDLINE | ID: covidwho-2223807

ABSTRACT

Epstein-Barr virus (EBV) reactivation in acute-phase of COVID-19 disease was recently discovered but it is not clear in terms of degree of mortality caused, and this was the aim of the current study. Six databases and three non-databases were thoroughly searched, independently. The articles related to non-human study (abstract, in vitro, in vivo, in silico, case study, poster, and review articles) were excluded for main analysis. Four articles related to mortality linked to EBV reactivation were systematically identified and included in the qualitative and quantitative analyses. Based on proportional meta-analysis of 4 studies, 34.3% or 0.343 (95% CI: 0.189-0.516; I 2 = 74.6) mortality related to EBV reactivation was identified. To address high heterogeneity, subgroup meta-analysis was carried out. Based on subgroup analysis, 26.6% or 0.266 (95% CI: 0.191-0.348; I 2 = 0) with no heterogeneity was identified. Interestingly, in comparative meta-analysis, EBV(-)/SARS-CoV-2(+) patients had statistically lesser mortality (9.9%) than EBV(+)/SARS-CoV-2(+) patients (23.6%) where RR = 2.31 (95% CI: 1.34-3.99; p = 0.003; I 2 = 6%). This finding is equivalent to the absolute mortality effect of 130 more per 1000 COVID-19 patients (95% CI: 34-296). Furthermore, based on statistical analysis, D-dimer was not statistically significantly different (p > 0.05) between the groups although studies have shown that D-dimer was statistically significantly different (p < 0.05) between these groups. Based on the inclusion and analysis of low risk of bias and high quality of articles graded with Newcastle-Ottawa Scale (NOS), when COVID-19 patients' health state is gradually worsening, EBV reactivation needs to be suspected because EBV reactivation is a possible marker for COVID-19 disease severity.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Humans , Herpesvirus 4, Human/physiology , Epstein-Barr Virus Infections/complications , SARS-CoV-2 , COVID-19/complications , Hospitalization
7.
Virol J ; 19(1): 50, 2022 03 19.
Article in English | MEDLINE | ID: covidwho-1841008

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
8.
Clin Chem ; 68(7): 953-962, 2022 07 03.
Article in English | MEDLINE | ID: covidwho-2188630

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.


Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Antibodies, Viral , DNA , DNA, Viral , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/genetics , Humans , Immunoglobulin A , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Neoplasms/diagnosis , Nasopharynx , Reflex , Triage
9.
Front Cell Infect Microbiol ; 12: 1016728, 2022.
Article in English | MEDLINE | ID: covidwho-2198712

ABSTRACT

Introduction: Patients with myasthenia gravis (MG) are prone to the development of pneumonia due to the long-term immunotherapies they receive and a tendency for aspiration. Pneumonia remains a risk factor for MG worsening and is the most prevalent cause of mortality in MG patients. Classification of the pathogens involved and exploration of the risk factors for mechanical ventilation (MV) could aid in improving clinical outcomes. Methods: Between January 2013 and October 2022, we performed an inpatient database review for MG patients with pneumonia concurrence in a tertiary research center specializing in neuromuscular disorders. The clinical and microbiological characteristics of 116 MG patients with pneumonia were retrospectively analyzed. Results: In our cohort, 90.32% (112/124) of organisms were bacteria and 42.86% (48/112) of pathogenic bacteria were carbapenem-resistant. A high abundance of Epstein-Barr virus (EBV) was detected using next-generation sequencing (NGS) in 12 patients, while cytomegalovirus (CMV) was detected in 8 patients. Non-fermentative Gram-negative bacilli were the most prevalent microorganisms, in which ampicillin, sulfamethoxazole-trimethoprim (SMZ-TMP), piperacillin, cefoperazone, ceftazidime, and cefepime may have an anti-infectious effect. Moreover, peripheral lymphocyte percentage [odds ratio (OR) 0.88, 95% CI 0.75-0.96, p = 0.02] and serum globulin (OR 1.16, 95% CI 1.02-1.35, p = 0.03) were significantly associated with the risk of MV demand. Discussion: Our identification of the microbial etiology of pneumonia in MG patients may provide future perspectives on accurate antibiotic options and enable early interventions when risk factors are present.


Subject(s)
Epstein-Barr Virus Infections , Myasthenia Gravis , Pneumonia , Humans , Retrospective Studies , Herpesvirus 4, Human , Anti-Bacterial Agents/therapeutic use , Pneumonia/drug therapy , Myasthenia Gravis/complications , Myasthenia Gravis/drug therapy , Microbial Sensitivity Tests
10.
BMJ Case Rep ; 15(12)2022 Dec 30.
Article in English | MEDLINE | ID: covidwho-2193663

ABSTRACT

A woman in her mid 40s presented for breast imaging after 1 week of painful and enlarged right axillary lymphadenopathy. She denied history of fever, weight loss, night sweats fatigue, cat scratch or other trauma. She received the second dose of Pfizer COVID-19 vaccine 3 months previously on the contralateral arm. A mammogram demonstrated a single, asymmetric, large and dense right axillary lymph node. Ultrasound confirmed a 2.5 cm lymph node with cortical thickening of 0.6 cm. Ultrasound-guided core biopsy showed necrotising lymphadenitis with associated aggregates of histiocytes and plasmacytoid dendritic cells. Potential causes of necrotising adenitis including Bartonella, tuberculosis, Epstein-Barr Virus, herpes simplex virus, systemic lupus erythematosus and lymphoma were excluded. In the absence of any identifiable infectious or autoimmune causes, and given the temporal relatedness with vaccine administration, it was determined that the Kikuchi-Fujimoto-like necrotising lymphadenitis was likely secondary to the COVID-19 vaccine. To date, there has been no casual association made between the COVID-19 vaccine and KFD necrotising lymphadenitis.


Subject(s)
COVID-19 Vaccines , COVID-19 , Epstein-Barr Virus Infections , Histiocytic Necrotizing Lymphadenitis , Lymphadenitis , Lymphadenopathy , Female , Humans , COVID-19/complications , COVID-19 Vaccines/adverse effects , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Histiocytic Necrotizing Lymphadenitis/etiology , Histiocytic Necrotizing Lymphadenitis/complications , Image-Guided Biopsy/adverse effects , Lymphadenopathy/etiology
11.
Sci Adv ; 9(1): eabq6978, 2023 01 04.
Article in English | MEDLINE | ID: covidwho-2193377

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although various viruses have been proposed to contribute to MS pathology, the etiology of MS remains unknown. Since intrathecal antibody synthesis is well documented in chronic viral infection and neuroinflammatory diseases, we hypothesized whether the patterns of antigen-specific antibody responses associated with various viral exposures may define patients with CNS chronic immune dysregulation. The pan-viral antibody profiling in cerebrospinal fluid (CSF) and serum of patients with MS showed significant differences from those in healthy volunteers and a pattern of antibody responses against multiple viruses, including the previously identified Epstein-Barr virus. These findings demonstrate that virus-specific antibody signatures might be able to reflect disease-associated inflammatory milieu in CSF of subjects with neuroinflammatory diseases.


Subject(s)
Epstein-Barr Virus Infections , Multiple Sclerosis , Humans , Herpesvirus 4, Human , Neuroinflammatory Diseases , Antiviral Agents
12.
Rinsho Ketsueki ; 63(11): 1513-1519, 2022.
Article in Japanese | MEDLINE | ID: covidwho-2155805

ABSTRACT

A 34-year-old man with no medical history presented with fever 4 days after receiving the first dose of mRNA-1273 coronavirus disease 2019 (COVID-19) vaccine. He had no prior clinical evidence of severe acute respiratory syndrome coronavirus 2 infection and was negative for serial polymerase chain reaction testing. Ten days after vaccination, he was referred to our hospital because of no response to antibiotics and the emergence of neutropenia, thrombocytopenia, and liver dysfunction. Blood tests also showed elevated serum ferritin and plasma soluble interleukin-2 receptors. Serological and PCR testing excluded active infections of cytomegalovirus, Epstein-Barr virus, and hepatitis viruses. Blood culture yielded no growth. Computed tomography revealed mild hepatosplenomegaly and porta hepatis lymphadenopathy but no focus on infection. Bone marrow aspiration demonstrated hemophagocytosis but no infiltrating lymphoma cells. Immediately, 2-mg/kg intravenous methylprednisolone was commenced based on the presumptive diagnosis of hemophagocytic lymphohistiocytosis (HLH), leading to the rapid and durable improvement of his symptoms and laboratory data. Later, without other causes triggering hemophagocytosis, and with the close link between vaccination and disease onset, the final diagnosis of vaccination-induced secondary HLH was made. HLH after COVID-19 vaccination, though extremely rare, can occur regardless of the vaccine type. Therefore, clinicians should recognize and deal with this occasionally fatal adverse event.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Humans , Adult , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , 2019-nCoV Vaccine mRNA-1273 , Herpesvirus 4, Human
13.
Sci Total Environ ; 864: 161023, 2023 Mar 15.
Article in English | MEDLINE | ID: covidwho-2159794

ABSTRACT

The early warning and tracking of COVID-19 prevalence in the community provided by wastewater surveillance has highlighted its potential for much broader viral disease surveillance. In this proof-of-concept study, 46 wastewater samples from four wastewater treatment plants (WWTPs) in Queensland, Australia, were analyzed for the presence and abundance of 13 respiratory viruses, and the results were compared with reported clinical cases. The viruses were concentrated using the adsorption-extraction (AE) method, and extracted nucleic acids were analyzed using qPCR and RT-qPCR. Among the viruses tested, bocavirus (BoV), parechovirus (PeV), rhinovirus A (RhV A) and rhinovirus B (RhV B) were detected in all wastewater samples. All the tested viruses except influenza B virus (IBV) were detected in wastewater sample from at least one WWTP. BoV was detected with the greatest concentration (4.96-7.22 log10 GC/L), followed by Epstein-Barr virus (EBV) (4.08-6.46 log10 GC/L), RhV A (3.95-5.63 log10 GC/L), RhV B (3.74-5.61 log10 GC/L), and PeV (3.17-5.32 log10 GC/L). Influenza viruses and respiratory syncytial virus (RSV) are notifiable conditions in Queensland, allowing the gene copy (GC) concentrations to be compared with reported clinical cases. Significant correlations (ρ = 0.60, p < 0.01 for IAV and ρ = 0.53, p < 0.01 for RSV) were observed when pooled wastewater influenza A virus (IAV) and RSV log10 GC/L concentrations were compared to log10 clinical cases among the four WWTP catchments. The positive predictive value for the presence of IAV and RSV in wastewater was 97 % for both IAV and RSV clinical cases within the four WWTP catchments. The overall accuracy of wastewater analysis for predicting clinical cases of IAV and RSV was 97 and 90 %, respectively. This paper lends credibility to the application of wastewater surveillance to monitor respiratory viruses of various genomic characteristics, with potential uses for increased surveillance capabilities and as a tool in understanding the dynamics of disease circulation in the communities.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Influenza, Human , Humans , Wastewater , Queensland/epidemiology , Herpesvirus 4, Human , Wastewater-Based Epidemiological Monitoring , Respiratory Syncytial Viruses/genetics , Influenza B virus/genetics , Australia , Influenza, Human/epidemiology
14.
BMC Ophthalmol ; 22(1): 462, 2022 Nov 30.
Article in English | MEDLINE | ID: covidwho-2139190

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) occasionally develop ocular complications. We report a case of acute retinal necrosis (ARN) caused by Epstein-Barr Virus (EBV) that developed in a patient who had severe acute respiratory syndrome due to SARS-CoV-2 infection. CASE PRESENTATION: A 68-year-old woman complained of floaters and blurred vision in her right eye as she was receiving systemic prednisolone for COVID-19 pneumonia under isolation in our hospital. The patient visited an ophthalmologist following her discharge from the hospital and after the 2 weeks of isolation had ended. At the initial examination, her best-corrected visual acuity (BCVA) was 20/100 in the right eye, and the eye showed moderate anterior segment inflammation and vitreous opacities. Treatment was initiated with topical 0.1% betamethasone and 1.5% levofloxacin. After 1 month, the inflammation in the right eye decreased and her BCVA improved to 20/40. However, on day 48 from her initial visit, the inflammation in her right eye worsened and her BCVA decreased to 20/2000 by day 80. Pars plana vitrectomy with silicone oil tamponade was performed to remove the vitreous opacities, and expanded white exudates peripherally and retinal vessels with white sheathing suggestive of acute retinal necrosis (ARN) were seen intraoperatively. Analysis of the vitreous sample revealed EBV positivity on polymerase chain reaction. The patient was diagnosed with EBV-associated ARN and treated with systemic steroids and valaciclovir. The ocular inflammation gradually decreased, and she was discharged from the hospital. However, a week later, the inflammation in the right eye markedly worsened. Despite another course of steroids, the inflammation worsened, resulting in total retinal detachment and absolute glaucoma. Because of the severe pain, the right eye was enucleated. CONCLUSIONS: Clinicians should be aware that COVID-19 and immunosuppressive treatment can reactivate EBV in the eye.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Pneumonia , Retinal Necrosis Syndrome, Acute , Humans , Female , Aged , Retinal Necrosis Syndrome, Acute/diagnosis , Retinal Necrosis Syndrome, Acute/drug therapy , Herpesvirus 4, Human , SARS-CoV-2 , Immunosuppressive Agents/adverse effects , Inflammation
15.
Lancet Oncol ; 23(12): e544-e551, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2132777

ABSTRACT

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Humans , Pandemics/prevention & control , Herpesvirus 4, Human , SARS-CoV-2 , Nasopharyngeal Carcinoma/therapy , DNA , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/therapy
16.
Cells ; 11(22)2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2116255

ABSTRACT

The scope of immune monitoring is to define the existence, magnitude, and quality of immune mechanisms operational in a host. In clinical trials and praxis, the assessment of humoral immunity is commonly confined to measurements of serum antibody reactivity without accounting for the memory B cell potential. Relying on fundamentally different mechanisms, however, passive immunity conveyed by pre-existing antibodies needs to be distinguished from active B cell memory. Here, we tested whether, in healthy human individuals, the antibody titers to SARS-CoV-2, seasonal influenza, or Epstein-Barr virus antigens correlated with the frequency of recirculating memory B cells reactive with the respective antigens. Weak correlations were found. The data suggest that the assessment of humoral immunity by measurement of antibody levels does not reflect on memory B cell frequencies and thus an individual's potential to engage in an anamnestic antibody response against the same or an antigenically related virus. Direct monitoring of the antigen-reactive memory B cell compartment is both required and feasible towards that goal.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Influenza, Human , Humans , SARS-CoV-2 , Herpesvirus 4, Human , Antibodies, Viral , Memory B Cells , Seasons
17.
J Gen Virol ; 103(11)2022 11.
Article in English | MEDLINE | ID: covidwho-2116873

ABSTRACT

Over the past few months there have been reports of severe acute hepatitis in several hundred, otherwise healthy, immunocompetent young children. Several deaths have been recorded and a relatively large proportion of the patients have needed liver transplants. Most of the cases, so far, have been seen in the UK and in North America, but it has also been reported in many other European countries, the Middle East and Asia. Most common viruses have been ruled out as a causative agent; hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) were not detected, nor were Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in many cases. A small proportion of the children had been infected with SARS-CoV-2 but these seem to be in a minority; similarly, almost none of the children had been vaccinated against COVID-19. Significantly, many of the patients were infected with adenovirus 41 (HAdV-F41). Previously, HAdV-41 had not been linked to hepatitis and is usually considered to cause gastroenteritis in both immunocompetent and immunocompromised patients. In two most recent studies, adeno-associated virus 2 (AAV2) was detected in almost all patients, together with species C and F HAdVs and human herpesvirus 6B (HHV6B). Here, I discuss the possibility that a change in tropism of HAdV-41 and changes in AAV2 may be responsible for their links to acute hepatitis.


Subject(s)
Adenoviridae Infections , COVID-19 , Epstein-Barr Virus Infections , Hepatitis , Parvovirinae , Child , Humans , Child, Preschool , Adenoviridae , Herpesvirus 4, Human , SARS-CoV-2 , Hepatitis/complications
18.
Front Immunol ; 13: 1029006, 2022.
Article in English | MEDLINE | ID: covidwho-2099152

ABSTRACT

T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Humans , Perforin/genetics , SARS-CoV-2 , Herpesvirus 4, Human , CD8-Positive T-Lymphocytes
19.
Viruses ; 14(9)2022 08 25.
Article in English | MEDLINE | ID: covidwho-2055385

ABSTRACT

Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein-Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Herpesvirus 6, Human , Herpesvirus 8, Human , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/physiology , Herpesvirus 6, Human/physiology , Humans , Inflammation , Inflammation Mediators
20.
Front Immunol ; 13: 915986, 2022.
Article in English | MEDLINE | ID: covidwho-2032772

ABSTRACT

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein-Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.


Subject(s)
Common Variable Immunodeficiency , Epstein-Barr Virus Infections , Hydroa Vacciniforme , Lymphoproliferative Disorders , Skin Neoplasms , Child , Common Variable Immunodeficiency/complications , Common Variable Immunodeficiency/therapy , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/therapy , Herpesvirus 4, Human , Humans , Hydroa Vacciniforme/diagnosis , Hydroa Vacciniforme/therapy , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/therapy
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