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1.
JCI Insight ; 7(6)2022 03 22.
Article in English | MEDLINE | ID: covidwho-1770087

ABSTRACT

Cytomegalovirus (CMV) is a globally ubiquitous pathogen with a seroprevalence of approximately 50% in the United Kingdom. CMV infection induces expansion of immunosenescent T cell and NK cell populations, with these cells demonstrating lower responsiveness to activation and reduced functionality upon infection and vaccination. In this study, we found that CMV+ participants had normal T cell responses after a single-dose or homologous vaccination with the viral vector chimpanzee adenovirus developed by the University of Oxford (ChAdOx1). CMV seropositivity was associated with reduced induction of IFN-γ-secreting T cells in a ChAd-Modified Vaccinia Ankara (ChAd-MVA) viral vector vaccination trial. Analysis of participants receiving a single dose of ChAdOx1 demonstrated that T cells from CMV+ donors had a more terminally differentiated profile of CD57+PD1+CD4+ T cells and CD8+ T cells expressing less IL-2Rα (CD25) and fewer polyfunctional CD4+ T cells 14 days after vaccination. NK cells from CMV-seropositive individuals also had a reduced activation profile. Overall, our data suggest that although CMV infection enhances immunosenescence of T and NK populations, it does not affect antigen-specific T cell IFN-γ secretion or antibody IgG production after vaccination with the current ChAdOx1 nCoV-19 vaccination regimen, which has important implications given the widespread use of this vaccine, particularly in low- and middle-income countries with high CMV seroprevalence.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Humans , Killer Cells, Natural , Seroepidemiologic Studies , Vaccination
3.
EBioMedicine ; 77: 103887, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1689314
4.
Int J Mol Sci ; 23(3)2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1686808

ABSTRACT

After solid-organ transplantation, reactivation of the cytomegalovirus (CMV) is often observed in seronegative patients and associated with a high risk of disease and mortality. CMV-specific T cells can prevent CMV reactivation. In a phase 1 trial, CMV-seronegative patients with end-stage renal disease listed for kidney transplantation were subjected to CMV phosphoprotein 65 (CMVpp65) peptide vaccination and further investigated for T-cell responses. To this end, CMV-specific CD8+ T cells were characterized by bulk T-cell-receptor (TCR) repertoire sequencing and combined single-cell RNA and TCR sequencing. In patients mounting an immune response to the vaccine, a common SYE(N)E TCR motif known to bind CMVpp65 was detected. CMV-peptide-vaccination-responder patients had TCR features distinct from those of non-responders. In a non-responder patient, a monoclonal inflammatory T-cell response was detected upon CMV reactivation. The identification of vaccine-induced CMV-reactive TCRs motifs might facilitate the development of cellular therapies for patients wait-listed for kidney transplantation.


Subject(s)
Cytomegalovirus Infections/prevention & control , Kidney Failure, Chronic/therapy , Receptors, Antigen, T-Cell/genetics , Viral Matrix Proteins/administration & dosage , CD8-Positive T-Lymphocytes/immunology , Clinical Trials, Phase I as Topic , Cytomegalovirus/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus Vaccines/administration & dosage , Cytomegalovirus Vaccines/immunology , Humans , Kidney Failure, Chronic/immunology , Kidney Transplantation , Sequence Analysis, RNA , Single Molecule Imaging , Viral Matrix Proteins/immunology
5.
Front Immunol ; 12: 784145, 2021.
Article in English | MEDLINE | ID: covidwho-1674332

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications.


Subject(s)
/adverse effects , Cytomegalovirus/drug effects , Pericarditis/chemically induced , SARS-CoV-2/immunology , Virus Activation/drug effects , Aged , Antiviral Agents/therapeutic use , COVID-19/prevention & control , Cytomegalovirus/physiology , Cytomegalovirus Infections/chemically induced , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Female , Humans , Pericarditis/drug therapy , Pericarditis/virology , Treatment Outcome , Valganciclovir/therapeutic use , Viremia/chemically induced , Viremia/drug therapy , Viremia/virology
6.
J Med Case Rep ; 16(1): 58, 2022 Jan 31.
Article in English | MEDLINE | ID: covidwho-1662424

ABSTRACT

BACKGROUND: The effect of coronavirus disease 2019 on the immune system is increasingly recognized. When severe, it causes immune dysregulation that may favor other infections, including Herpesviridae. Cytomegalovirus shares many innate immune pathways with severe acute respiratory syndrome coronavirus 2, which may potentiate each other. We describe a case of cytomegalovirus pneumonitis complicating the course of coronavirus disease 2019 in a patient with systemic lupus erythematosus/systemic sclerosis overlap and usual interstitial pneumonia, mimicking interstitial lung disease exacerbation. To the best of the authors' knowledge, this is the first case to be reported worldwide in the setting of connective tissue disease-associated interstitial lung disease. CASE DESCRIPTION: We describe the case of a 47-year-old white/Yemeni female who is known to have systemic lupus erythematosus/scleroderma overlap and usual interstitial pneumonia who was initially admitted with severe coronavirus disease 2019 pneumonia mandating intensive care. After initial improvement, it was later complicated with cytomegalovirus pneumonitis, mimicking interstitial lung disease exacerbation. The case was successfully treated with ganciclovir. CONCLUSION: Intriguingly, severe acute respiratory syndrome coronavirus 2 and cytomegalovirus may potentiate each other, since they share some innate immune pathways. Subjects with severe coronavirus disease 2019 and underlying connective tissue diseases and those who are immunosuppressed carry higher risk compared with other cohorts, which may mandate active surveillance for cytomegalovirus coinfection or reactivation. Among various immunosuppressive therapies that has been tried for cytokine storm, use of anti-interleukin-6 inhibitors in the aforementioned population may carry more harm than previously thought, which may suggest that is reasonable to omit its use in treating this group with coronavirus disease 2019. This case underlines an underrecognized and underreported cause of morbidity and mortality during the course of severe coronavirus disease 2019 and will help to alert clinicians of its occurrence.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Pneumonia , Cytomegalovirus , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Female , Humans , Middle Aged , SARS-CoV-2
8.
Indian J Ophthalmol ; 70(1): 323-326, 2022 01.
Article in English | MEDLINE | ID: covidwho-1594596

ABSTRACT

A 62-year-old female diabetic recovered from COVID-19 pneumonia after receiving a prolonged course of steroids. She presented with a clinical picture of left-eye panuveitis with white cotton ball chorioretinal lesions and RAPD suggesting an optic neuropathy (VA HM). Diagnostic vitrectomy was performed to take samples for infective screen and to give intravitreal voriconazole empirically. Smear, culture, and PCR for viral DNA confirmed mixed infection of endogenous Candida endophthalmitis and incidental CMV infection. With further treatment, her corrected vision improved to 6/18 with regressing fungal lesions in serial fundus photographs. Prompt diagnosis and intervention preserved her vision and prevented potential life-threatening complications.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Endophthalmitis , Eye Infections, Fungal , Optic Nerve Diseases , Antifungal Agents/therapeutic use , Candida , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Eye Infections, Fungal/complications , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Female , Humans , Middle Aged , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/drug therapy , Optic Nerve Diseases/etiology , Random Amplified Polymorphic DNA Technique , SARS-CoV-2 , Vitrectomy
9.
Expert Rev Anti Infect Ther ; 20(5): 663-680, 2022 May.
Article in English | MEDLINE | ID: covidwho-1545821

ABSTRACT

INTRODUCTION: In solid organ transplant (SOT) recipients, viral infections are associated with direct morbidity and mortality and may influence long-term allograft outcomes. Prevention of viral infections by vaccination, antiviral prophylaxis, and behavioral measures is therefore of paramount importance. AREAS COVERED: We searched Pubmed to select publications to review current preventive strategies against the most important viral infections in SOT recipients, including SARS-CoV-2, influenza, CMV, and other herpesvirus, viral hepatitis, measles, mumps, rubella, and BK virus. EXPERT OPINION: The clinical significance of the reduced humoral response following mRNA SARS-CoV-2 vaccines in SOT recipients still needs to be better clarified, in particular with regard to the vaccines' efficacy in preventing severe disease. Although a third dose improves immunogenicity and is already integrated into routine practice in several countries, further research is still needed to explore additional interventions. In the upcoming years, further data are expected to better delineate the role of virus-specific cell mediated immune monitoring for the prevention of CMV and potentially other viral diseases, and the role of the letermovir in the prevention of CMV in SOT recipients. Future studies including clinical endpoints will hopefully facilitate the integration of successful new influenza vaccination strategies into clinical practice.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Influenza, Human , Organ Transplantation , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines , Cytomegalovirus Infections/prevention & control , Humans , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients
10.
Pak J Biol Sci ; 24(11): 1169-1174, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1542850

ABSTRACT

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , Calcifediol/blood , Herpes Simplex/diagnosis , Herpesvirus 1, Human/immunology , Immunoglobulin G/blood , Vitamin D Deficiency/diagnosis , Adaptive Immunity , Adult , Biomarkers/blood , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , Cytomegalovirus/immunology , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/immunology , Female , Herpes Simplex/blood , Herpes Simplex/epidemiology , Herpes Simplex/immunology , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Rubella/blood , Rubella/diagnosis , Rubella/epidemiology , Rubella/immunology , Rubella virus/immunology , Saudi Arabia/epidemiology , Seroepidemiologic Studies , Streptococcal Infections/blood , Streptococcal Infections/diagnosis , Streptococcal Infections/epidemiology , Streptococcal Infections/immunology , Streptococcus/immunology , Toxoplasma/immunology , Toxoplasmosis/blood , Toxoplasmosis/diagnosis , Toxoplasmosis/epidemiology , Toxoplasmosis/immunology , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology
11.
Int J Mol Sci ; 22(22)2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1524028

ABSTRACT

Aging is characterized by the dynamic remodeling of the immune system designated "immunosenescence," and is associated with altered hematopoiesis, thymic involution, and lifelong immune stimulation by multitudinous chronic stressors, including the cytomegalovirus (CMV). Such alterations may contribute to a lowered proportion of naïve T-cells and to reduced diversity of the T-cell repertoire. In the peripheral circulation, a shift occurs towards accumulations of T and B-cell populations with memory phenotypes, and to accumulation of putatively senescent and exhausted immune cells. The aging-related accumulations of functionally exhausted memory T lymphocytes, commonly secreting pro-inflammatory cytokines, together with mediators and factors of the innate immune system, are considered to contribute to the low-grade inflammation (inflammaging) often observed in elderly people. These senescent immune cells not only secrete inflammatory mediators, but are also able to negatively modulate their environments. In this review, we give a short summary of the ways that immunosenescence, inflammaging, and CMV infection may cause insufficient immune responses, contribute to the establishment of the hyperinflammatory syndrome and impact the severity of the coronavirus disease 2019 (COVID-19) in elderly people.


Subject(s)
COVID-19/pathology , Aging , B-Lymphocytes/pathology , COVID-19/complications , COVID-19/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/pathology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/pathology , Cytomegalovirus Infections/virology , Humans , SARS-CoV-2/isolation & purification , T-Lymphocytes/pathology
12.
J Autoimmun ; 124: 102727, 2021 11.
Article in English | MEDLINE | ID: covidwho-1446793

ABSTRACT

Systemic sclerosis (SSc) is a connective tissue disease secondary to three cardinal pathological features: immune-system alterations, diffuse microangiopathy, and fibrosis involving the skin and internal organs. The etiology of SSc remains quite obscure; it may encompass multiple host genetic and environmental -infectious/chemical-factors. The present review focused on the potential role of environmental agents in the etiopathogenesis of SSc based on epidemiological, clinical, and laboratory investigations previously published in the world literature. Among infectious agents, some viruses that may persist and reactivate in infected individuals, namely human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and parvovirus B19 (B19V), and retroviruses have been proposed as potential causative agents of SSc. These viruses share a number of biological activities and consequent pathological alterations, such as endothelial dysfunction and/or fibroblast activation. Moreover, the acute worsening of pre-existing interstitial lung involvement observed in SSc patients with symptomatic SARS-CoV-2 infection might suggest a potential role of this virus in the overall disease outcome. A variety of chemical/occupational agents might be regarded as putative etiological factors of SSc. In this setting, the SSc complicating silica dust exposure represents one of the most promising models of study. Considering the complexity of SSc pathogenesis, none of suggested causative factors may explain the appearance of the whole SSc; it is likely that the disease is the result of a multifactorial and multistep pathogenetic process. A variable combination of potential etiological factors may modulate the appearance of different clinical phenotypes detectable in individual scleroderma patients. The in-deep investigations on the SSc etiopathogenesis may provide useful insights in the broad field of human diseases characterized by diffuse microangiopathy or altered fibrogenesis.


Subject(s)
COVID-19/complications , Cytomegalovirus Infections/complications , Occupational Exposure/adverse effects , Parvoviridae Infections/complications , Retroviridae Infections/complications , Roseolovirus Infections/complications , SARS-CoV-2 , Scleroderma, Systemic/etiology , Cytomegalovirus , Herpesvirus 6, Human , Humans , Parvovirus B19, Human , Retroviridae , Scleroderma, Systemic/virology
13.
Eur J Pediatr ; 181(3): 1259-1262, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1446162

ABSTRACT

Cytomegalovirus (CMV) is the most frequent cause of congenital infection all over the world. Its prevalence ranges from 0.2 to 2.2%. Transmission from children to their pregnant mothers is a well-known risk factor, particularly if they attend a childcare centre. This study aims to compare the prevalence of CMV congenital infection (CMV_CI) in Portugal (Lisbon) between two studies, performed respectively in 2019 and 2020. In the 2019 study, performed in two hospitals, we found a 0.67% CMV_CI prevalence, using a pool strategy previously tested with saliva samples. In the 2020 study, using the same pool approach in four hospitals (the previous and two additional), and based on 1277 samples, the prevalence was 0.078%.Conclusion: The close temporal coincidence with COVID-19 lockdown suggests that these measures may have had a significant impact on this reduction, although other explanations cannot be ruled-out. What is Known: • Cytomegalovirus is the leading cause of congenital infection. • Behavioural measures decrease cytomegalovirus seroconversion in pregnant women. What is New: • From 2019 to 2020 there was a significant reduction in the prevalence of congenital CMV infection.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Pregnancy Complications, Infectious , COVID-19/epidemiology , COVID-19/prevention & control , Child , Communicable Disease Control , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/prevention & control , Female , Humans , Portugal/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , Prevalence , SARS-CoV-2
14.
Curr HIV Res ; 19(6): 548-551, 2021.
Article in English | MEDLINE | ID: covidwho-1381330

ABSTRACT

BACKGROUND: The current COVID-19 pandemic has attracted great attention from the medical world. In the past year, there have been reports of missed or delayed treatments for conditions that mimic COVID-19. The main symptoms caused by SARS-CoV-2, such as fever and cough, belong to different clinical conditions. It is of the utmost importance that the diagnostic thinking used to analyze data and information to reach a COVID-19 diagnosis does not overlook the plethora of different diagnoses related to these symptoms. CASE REPORT: The aim of this work is to present the clinical case of a patient having unrecognized HIV infection with a 4-week history of fever, cough, and hypoxia. When tests were allowed to highlight HIV-related immunodeficiency status, a CMV assay was performed in order to evaluate opportunistic pneumonia. Through this, diagnosis of HIV combined with CMV pneumonia was made, thus excluding COVID-19 respiratory insufficiency. CONCLUSION: The diagnosis of the two conditions in the COVID-19 era is challenging due to overlapping clinical and radiological features and limitations of current diagnostic assays. This causes clinical implications due to diagnostic delays.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Cytomegalovirus Infections/diagnosis , Dyspnea/virology , HIV Infections/diagnosis , Pneumonia, Viral/diagnosis , COVID-19 , COVID-19 Testing , Diagnosis, Differential , Humans , Male , Middle Aged
15.
PLoS One ; 16(8): e0249484, 2021.
Article in English | MEDLINE | ID: covidwho-1379827

ABSTRACT

The human adaptive immune system must generate extraordinary diversity to be able to respond to all possible pathogens. The T-cell repertoire derives this high diversity through somatic recombination of the T-cell receptor (TCR) locus, a random process that results in repertoires that are largely private to each individual. However, factors such as thymic selection and T-cell proliferation upon antigen exposure can affect TCR sharing among individuals. By immunosequencing the TCRß variable region of 426 healthy individuals, we find that, on average, fewer than 1% of TCRß clones are shared between individuals, consistent with largely private TCRß repertoires. However, we detect a significant correlation between increased HLA allele sharing and increased number of shared TCRß clones, with each additional shared HLA allele contributing to an increase in ~0.01% of the total shared TCRß clones, supporting a key role for HLA type in shaping the immune repertoire. Surprisingly, we find that shared antigen exposure to CMV leads to fewer shared TCRß clones, even after controlling for HLA, indicative of a largely private response to major viral antigenic exposure. Consistent with this hypothesis, we find that increased age is correlated with decreased overall TCRß clone sharing, indicating that the pattern of private TCRß clonal expansion is a general feature of the T-cell response to other infectious antigens as well. However, increased age also correlates with increased sharing among the lowest frequency clones, consistent with decreased repertoire diversity in older individuals. Together, all of these factors contribute to shaping the TCRß repertoire, and understanding their interplay has important implications for the use of T cells for therapeutics and diagnostics.


Subject(s)
HLA Antigens/immunology , Histocompatibility Testing , Receptors, Antigen, T-Cell/immunology , Virus Diseases/immunology , Adult , Age Factors , Chronic Disease , Cytomegalovirus Infections/immunology , Histocompatibility Testing/methods , Humans
16.
Int J Antimicrob Agents ; 58(4): 106409, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330851

ABSTRACT

Since the start of the COVID-19 pandemic, there has been concern about the concomitant rise of antimicrobial resistance. While bacterial co-infections seem rare in COVID-19 patients admitted to hospital wards and intensive care units (ICUs), an increase in empirical antibiotic use has been described. In the ICU setting, where antibiotics are already abundantly-and often inappropriately-prescribed, the need for an ICU-specific antimicrobial stewardship programme is widely advocated. Apart from essentially warning against the use of antibacterial drugs for the treatment of a viral infection, other aspects of ICU antimicrobial stewardship need to be considered in view of the clinical course and characteristics of COVID-19. First, the distinction between infectious and non-infectious (inflammatory) causes of respiratory deterioration during an ICU stay is difficult, and the much-debated relevance of fungal and viral co-infections adds to the complexity of empirical antimicrobial prescribing. Biomarkers such as procalcitonin for the decision to start antibacterial therapy for ICU nosocomial infections seem to be more promising in COVID-19 than non-COVID-19 patients. In COVID-19 patients, cytomegalovirus reactivation is an important factor to consider when assessing patients infected with SARS-CoV-2 as it may have a role in modulating the patient immune response. The diagnosis of COVID-19-associated invasive aspergillosis is challenging because of the lack of sensitivity and specificity of the available tests. Furthermore, altered pharmacokinetic/pharmacodynamic properties need to be taken into account when prescribing antimicrobial therapy. Future research should now further explore the 'known unknowns', ideally with robust prospective study designs.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/methods , COVID-19 , Cross Infection/diagnosis , Anti-Bacterial Agents/pharmacokinetics , Antimicrobial Stewardship/organization & administration , Biomarkers/analysis , COVID-19/drug therapy , Coinfection/drug therapy , Coinfection/microbiology , Cross Infection/drug therapy , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Virus Activation/drug effects
17.
J Infect Dis ; 225(3): 443-452, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1307535

ABSTRACT

BACKGROUND: Evaluating age as a risk factor for susceptibility to infectious diseases, particularly coronavirus disease 2019 (COVID-19), is critical. Cytomegalovirus (CMV) serologic prevalence increases with age and associates with inflammatory-mediated diseases in the elderly. However, little is known regarding the subclinical impact of CMV and risk it poses to healthy older adults. Prior to the COVID-19 pandemic we conducted a study to determine the association of CMV to biologic age and immune dysregulation. METHODS: Community-dwelling, healthy adults older than 60 years were evaluated using DNA methylation assays to define epigenetic age (EpiAge) and T-cell immunophenotyping to assess immune dysregulation. RESULTS: All subjects were healthy and asymptomatic. Those CMV seropositive had more lymphocytes, CD8 T cells, CD28- T cells, decreased CD4:CD8 cell ratios, and had higher average EpiAge (65.34 years) than those CMV seronegative (59.53 years). Decreased percent CD4 (P = .003) and numbers of CD4 T cells (P = .0199) correlated with increased EpiAge. CONCLUSIONS: Our novel findings distinguish altered immunity in the elderly based on CMV status. Chronic CMV infection in healthy, older adults is associated with indicators of immune dysregulation, both of which correlate to differences in EpiAge.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cytomegalovirus Infections , Epigenesis, Genetic , Aged , Asymptomatic Infections , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/immunology , DNA Methylation , Humans , Middle Aged
19.
Transpl Immunol ; 68: 101435, 2021 10.
Article in English | MEDLINE | ID: covidwho-1294281

ABSTRACT

Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to "isolation ward" due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.


Subject(s)
Antifungal Agents/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Carcinoma, Hepatocellular/therapy , Cytomegalovirus Infections , Cytomegalovirus , Graft vs Host Disease/drug therapy , Liver Neoplasms/therapy , Liver Transplantation , SARS-CoV-2 , Acute Disease , Cytomegalovirus Infections/drug therapy , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/virology , Humans , Male , Middle Aged
20.
Viruses ; 13(7)2021 06 29.
Article in English | MEDLINE | ID: covidwho-1289029

ABSTRACT

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still exhibit increased morbidity and mortality compared to the general population. Such differences in health outcomes are related to higher risk behaviors, but also to HIV-related immune activation and viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection is a well-known inducer of long-term immune dysregulation. Cytomegalovirus contributes to the persistent immune activation in PLWH receiving ART by directly skewing immune response toward itself, and by increasing immune activation through modification of the gut microbiota and microbial translocation. In addition, through induction of immunosenescence, CMV has been associated with a decreased response to infections and vaccines. This review provides a comprehensive overview of the influence of CMV on the immune system, the mechanisms underlying a reduced response to vaccines, and discuss new therapeutic advances targeting CMV that could be used to improve vaccine response in PLWH.


Subject(s)
Coinfection/virology , Cytomegalovirus Infections/virology , Cytomegalovirus/immunology , HIV Infections/virology , Vaccines/immunology , Animals , Anti-HIV Agents/therapeutic use , Clinical Trials as Topic , Cytomegalovirus/pathogenicity , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/immunology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/pathology , Gastrointestinal Tract/virology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Immunosenescence , Inflammation , Latent Infection/immunology , Latent Infection/virology , Mice , Vaccines/administration & dosage
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