Transient Decrease in Incidence Rate of Maternal Primary Cytomegalovirus Infection during the COVID-19 Pandemic in Japan.

This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of maternal primary cytomegalovirus (CMV) infection in Japan. We performed a nested case-control study using data from maternal CMV antibody screening under the Cytomegalovirus in Mother and infant-engaged Virus serology (CMieV) program in Mie, Japan. Pregnant women with negative IgG antibodies at ≤20 weeks of gestation who were retested at ≥28 weeks were enrolled. The study period was divided into 2015-2019 as the pre-pandemic and 2020-2022 as the pandemic period, and the study site included 26 institutions conducting the CMieV program. The incidence rate of maternal IgG seroconversion was compared between the pre-pandemic (7008 women enrolled) and pandemic (2020, 1283 women enrolled; 2021, 1100 women; and 2022, 398 women) periods. Sixty-one women in the pre-pandemic period and five, four, and five women during 2020, 2021, and 2022, respectively, showed IgG seroconversion. The incidence rates in 2020 and 2021 were lower (p < 0.05) than that in the pre-pandemic period. Our data suggest a transient decrease in the incidence of maternal primary CMV infection in Japan during the COVID-19 pandemic, which could be due to prevention and hygiene measures taken at the population level.

Applying T-classifier, binary classifiers, upon high-throughput TCR sequencing output to identify cytomegalovirus exposure history.

With the continuous development of information technology and the running speed of computers, the development of informatization has led to the generation of increasingly more medical data. Solving unmet needs such as employing the constantly developing artificial intelligence technology to medical data and providing support for the medical industry is a hot research topic. Cytomegalovirus (CMV) is a kind of virus that exists widely in nature with strict species specificity, and the infection rate among Chinese adults is more than 95%. Therefore, the detection of CMV is of great importance since the vast majority of infected patients are in a state of invisible infection after the infection, except for a few patients with clinical symptoms. In this study, we present a new method to detect CMV infection status by analyzing high-throughput sequencing results of T cell receptor beta chains (TCRß). Based on the high-throughput sequencing data of 640 subjects from cohort 1, Fisher's exact test was performed to evaluate the relationship between TCRß sequences and CMV status. Furthermore, the number of subjects with these correlated sequences to different degrees in cohort 1 and cohort 2 were measured to build binary classifier models to identify whether the subject was CMV positive or negative. We select four binary classification algorithms: logistic regression (LR), support vector machine (SVM), random forest (RF), and linear discriminant analysis (LDA) for side-by-side comparison. According to the performance of different algorithms corresponding to different thresholds, four optimal binary classification algorithm models are obtained. The logistic regression algorithm performs best when Fisher's exact test threshold is 10-5, and the sensitivity and specificity are 87.5% and 96.88%, respectively. The RF algorithm performs better at the threshold of 10-5, with a sensitivity of 87.5% and a specificity of 90.63%. The SVM algorithm also achieves high accuracy at the threshold value of 10-5, with a sensitivity of 85.42% and specificity of 96.88%. The LDA algorithm achieves high accuracy with 95.83% sensitivity and 90.63% specificity when the threshold value is 10-4. This is probably because the two-dimensional distribution of CMV data samples is linearly separable, and linear division models such as LDA are more effective, while the division effect of nonlinear separable algorithms such as random forest is relatively inaccurate. This new finding may be a potential diagnostic method for CMV and may even be applicable to other viruses, such as the infectious history detection of the new coronavirus.

Cytomegalovirus Management in Solid Organ Transplant Recipients: A Pre-COVID-19 Survey From the Working Group of the European Society for Organ Transplantation.

Infections are leading causes of morbidity/mortality following solid organ transplantation (SOT) and cytomegalovirus (CMV) is among the most frequent pathogens, causing a considerable threat to SOT recipients. A survey was conducted 19 July-31 October 2019 to capture clinical practices about CMV in SOT recipients (e.g., how practices aligned with guidelines, how adequately treatments met patients' needs, and respondents' expectations for future developments). Transplant professionals completed a ∼30-minute online questionnaire: 224 responses were included, representing 160 hospitals and 197 SOT programs (41 countries; 167[83%] European programs). Findings revealed a heterogenous approach to CMV diagnosis and management and, sometimes, significant divergence from international guidelines. Valganciclovir prophylaxis (of variable duration) was administered by 201/224 (90%) respondents in D+/R- SOT and by 40% in R+ cases, with pre-emptive strategies generally reserved for R+ cases: DNA thresholds to initiate treatment ranged across 10-10,000 copies/ml. Ganciclovir-resistant CMV strains were still perceived as major challenges, and tailored treatment was one of the most important unmet needs for CMV management. These findings may help to design studies to evaluate safety and efficacy of new strategies to prevent CMV disease in SOT recipients, and target specific educational activities to harmonize CMV management in this challenging population.

Impact of the COVID-19 Pandemic on the Diagnosis of Congenital Cytomegalovirus Infection in Spain.

We conducted an observational study performed within the Spanish Registry of Children with congenital cytomegalovirus (cCMV) to evaluate the impact of the COVID-19 pandemic on the diagnosis of new cases of cCMV. Our study suggest a significant decrease in the monthly rate of new cCMV diagnoses during the COVID-19 pandemic.

Cytomegalovirus pneumonitis amid COVID-19 chaos: the hidden enemy-a case report.

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.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<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.

It is Not Always COVID-19: Case Report about an Undiagnosed HIV Man with Dyspnea.

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.

Are the Healthy Vulnerable? Cytomegalovirus Seropositivity in Healthy Adults Is Associated With Accelerated Epigenetic Age and Immune Dysregulation.

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.

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus.

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal­neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.

Misleading Diagnosis of Radiological Imaging of COVID-19 Pneumonia During Pandemic Era: Risk on the Existence of CMV Infection.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease which rapidly disseminated due to Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) virus. Clinical presentations of COVID-19 are fever, non-productive cough, and dyspnea. Although the diagnosis establishment is done by detecting the viral ribonucleic acid (RNA) through reverse transcription-polymerase chain reaction (RT-PCR) method, CT scan has an important role in detection and treatment of COVID-19 especially in high prevalence regions. Chest CT scan has high sensitivity yet low specificity because there are a lot of other pathological spectrums that also present features of COVID-19 such as ground glass opacities (GGO) and consolidation, one of them is CMV infection. The objective of this case report is to raise vigilance towards other diseases that have radiological image similarities with COVID-19, especially in the immunocompromised patients who are susceptible to viral infections like CMV infection so that the delay in the disease treatment can be prevented.

A misleading CMV myocarditis during the COVID-19 pandemic: case report.

Coronavirus disease 2019 (COVID-19) has been reported as the possible cause of acute myocarditis. Myocarditis is an inflammatory heart disease mostly caused by viral infections. Cytomegalovirus (CMV) primary infection is often not suspected as a cause of myocarditis in immune-competent adults. We report the case of a 37-year-old male admitted with fever, cough and dyspnea. Chest CT showed typical ground-glass changes indicative of viral pneumonia. He was tested negative for COVID-19 but had biological markers that made us still suspect it. He had elevated troponin I level (up to 111.5 ng/mL) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF). He was diagnosed with CMV myocarditis with cardiac insufficiency and totally recovered without antiviral therapy. During the COVID-19 pandemic patients may develop myocarditis, still every myocarditis is not a COVID infection. Myocarditis linked to CMV infection may be rare, but life-threatening.