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.

Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment.

Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic.

Systemic Viral Infections and the Eye

Ocular manifestations of systemic viral infections are common. Because viral infection syndromes may be nonspecific, diagnosis of a particular viral infection often requires understanding of the risk factors and transmission modes of viral pathogens. Careful review of both history of the disease and the ocular exam findings can be helpful in narrowing down the differential diagnosis for the systemic condition and vice versa. A history of exposures, including animal exposures, sexual exposures, and travel, as well as the vaccination history and general medical history helps guide the workup and treatment of viral infections. Diagnostic testing for viral infections may include blood testing for serologic studies and viral detection, samples from involved extraocular organs, as well as ocular samples that can confirm a diagnosis and facilitate initiation of optimal therapy while minimizing side effects from exposure to unnecessary antiviral agents. Importantly, patients with HIV or other immunocompromising conditions may simultaneously have more than one active infection and also may manifest with syndromes that are atypical and have serologic testing that is less accurate. Careful and aggressive diagnostic evaluation of ocular symptoms is especially important in these patients, as are efforts to improve immune function while monitoring for the possible impact of immune reconstitution on the clinical course. © Springer Nature Switzerland AG 2022.

Medical diagnostic value of digital PCR (dPCR): A systematic review

Digital polymerase chain reaction (dPCR) is an emerging technique for the absolute quantification of target nucleic acids. dPCR got attention as a precise quantification tool in preclinical research, particularly when used to detect genetic mutations and result in highly precise measurements. In dPCR, the statistic of Poisson distribution was followed for the random distribution of molecules in different partitions, which is essential for dPCR quantification. Amplified target sequences in different partitions are identified by fluorescence and each partition functions as a separate PCR microreactor. Without the need for calibration, the percentage of PCR-positive partitions is sufficient to estimate the concentration of the target sequence. The present revolution in digital quantification was made possible by advancements in microfluidics, which provided effective partitioning techniques. In this paper, the contrast of the underlying ideas of quantitative real-time PCR with dPCR for the measurement of nucleic acids quantity Polymerase chain reaction (q-PCR). This review study briefly introduced the background of dPCR and compared different types of PCR, particularly the quantity of real-time qPCR and digital PCR. The fundamental concept of dPCR is also explained and also briefly compares the advantages of dPCR over qPCR and analyzes the applications of dPCR as a diagnostic tool for cancer and different types of viral species.

Epstein-Barr virus and cytomegalovirus coinfection in Egyptian COVID-19 patients.

Background: Reactivation of herpesviruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in COVID-19 patients reported in many studies in different countries during the pandemic. We aimed to measure prevalence of this coinfection in Egyptian COVID-19 patients with elevated liver enzymes and its relation to the severity and the outcome of COVID-19 infection in those patients. Methods: A cross-sectional study was carried out on 110 COVID-19 patients with elevated liver enzymes regardless the severity of COVID-19 disease. All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest). Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) were determined by VCA IgM and CMV IgM respectively by enzyme-linked immunosorbent assay (ELISA). Results: Of the included 110 patients with COVID-19 illness, 5 (4.5%) were Epstein-Barr virus seropositive and 5 (4.5%) were human cytomegalovirus seropositive. Regarding the symptoms, the incidence of fever in the EBV and CMV seropositive group was apparently higher than that in the EBV and CMV seronegative group. In lab tests, the platelets and albumin of EBV and CMV seropositive group decreased more significantly than EBV and HCMV seronegative group, and serum ferritin, D-dimer, and C-reactive protein show higher values in seropositive group than in seronegative group but not statistically significant. Seropositive group had received higher doses of steroids than seronegative group. The median of hospital stay in seropositive group was (15 days) nearly double that of seronegative group with statistically significant difference between both groups. Conclusion: Coinfection of EBV and CMV in COVID-19 Egyptian has no effect on the disease severity or the clinical outcome of the disease. But those patients had higher hospital stay duration.

Systematic review with meta-analysis of active herpesvirus infections in patients with COVID-19: Old players on the new field.

OBJECTIVES: Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences could be triggered by other infection. Therefore, reactivation of herpesviruses in COVID-19 patients represents an emerging issue. DESIGN AND METHODS: This study provided the first systematic review with meta-analysis of studies that evaluated active human herpesvirus (HHV) infection (defined as the presence of IgM antibodies or HHV-DNA) in COVID-19 patients and included 36 publications collected by searching through PubMed, SCOPUS, and Web of science until November 2022. RESULTS: The prevalence of active EBV, HHV6, HSV, CMV, HSV1, and VZV infection in COVID-19 population was 41% (95% CI =27%-57%), 3% (95% CI=17%-54%), 28% (95% CI=1%-85%), 25% (95% CI=1%-63%), 22% (95% CI=10%-35%), and 18% (95% CI=4%-34%), respectively. There was a 6 times higher chance for active EBV infection in patients with severe COVID-19 than in non-COVID-19 controls (OR=6.45, 95% CI=1.09-38.13, p=0.040), although there was no difference in the prevalence of all evaluated active herpesvirus infections between COVID-19 patients and non-COVID-19 controls. CONCLUSIONS: Future research of herpesvirus and SARS-CoV-2 coinfections must be prioritized to define: who, when and how to be tested, as well as how to effectively treat HHVs reactivations in acute and long COVID-19 patients.

Cytomegalovirus reactivation with high viral load in a patient of coronavirus disease 2019 acute respiratory distress syndrome: a case report.

INTRODUCTION: Cytomegalovirus establishes life-long latency after primary infection in childhood. Cytomegalovirus reactivation has been well reported in immune-compromised patients; however, in the last few years it has been observed that cytomegalovirus reactivation also occurs in critically ill patients without exogenous immunosuppression, which increases length of intensive care unit stay and mortality rate. CASE REPORT: A 63-year-old Indian male, without any known comorbidity, developed severe coronavirus disease 2019 and was admitted to the intensive care unit. He received remdesivir, tocilizumab, steroids, anticoagulants, and empiric antibiotics over the next 3 weeks. However, his clinical condition did not improve much, and during the 9th week of illness his condition started deteriorating and routine bacterial cultures, fungal cultures, and cytomegalovirus real-time polymerase chain reaction on blood were negative. His clinical condition worsened rapidly, which led to the need for invasive mechanical ventilation. Tracheal aspirate bacterial and fungal culture showed no growth, but cytomegalovirus real-time polymerase chain reaction showed 21,86,000 copies/mL in tracheal aspirates. After 4 weeks of ganciclovir treatment, the patient improved clinically and was discharged. Currently he is doing well and able to do his routine activity without the need of oxygen. CONCLUSION: Timely management with ganciclovir is associated with favorable outcome in cytomegalovirus infection. Thus, it can be suggested that treatment should be initiated with ganciclovir if a patient with coronavirus disease 2019 has high cytomegalovirus load in tracheal aspirates, along with unexplained and prolonged clinical and/or radiological features.

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections.

Progress in stem cell research has revolutionized the medical field for more than two decades. More recently, the discovery of induced pluripotent stem cells (iPSCs) has allowed for the development of advanced disease modeling and tissue engineering platforms. iPSCs are generated from adult somatic cells by reprogramming them into an embryonic-like state via the expression of transcription factors required for establishing pluripotency. In the context of the central nervous system (CNS), iPSCs have the potential to differentiate into a wide variety of brain cell types including neurons, astrocytes, microglial cells, endothelial cells, and oligodendrocytes. iPSCs can be used to generate brain organoids by using a constructive approach in three-dimensional (3D) culture in vitro. Recent advances in 3D brain organoid modeling have provided access to a better understanding of cell-to-cell interactions in disease progression, particularly with neurotropic viral infections. Neurotropic viral infections have been difficult to study in two-dimensional culture systems in vitro due to the lack of a multicellular composition of CNS cell networks. In recent years, 3D brain organoids have been preferred for modeling neurotropic viral diseases and have provided invaluable information for better understanding the molecular regulation of viral infection and cellular responses. Here we provide a comprehensive review of the literature on recent advances in iPSC-derived 3D brain organoid culturing and their utilization in modeling major neurotropic viral infections including HIV-1, HSV-1, JCV, ZIKV, CMV, and SARS-CoV2.

Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry.

Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.

Cytomegalovirus pneumonitis in infants: The challenge in diagnosis among pediatricians.

Cytomegalovirus (CMV) pneumonitis infections might present mild or severe illnesses and need sophisticated diagnostic tools, so it remains a diagnostic challenge. We reported five infants diagnosed with CMV pneumonitis who were initially and undiagnosed by the pediatrician in secondary private or public health hospitals with no improvement with standard and escalation of antibiotics treatment for bronchopneumonia as the initial diagnoses. As all cases occurred during the COVID-19 pandemic, they proved negative COVID-19 identified by polymerase chain reaction (PCR) SARS-CoV-2. We diagnosed acquired perinatal pneumonitis CMV in all claims based on clinical criteria, imaging studies, CMV serology, and PCR-CMV urinary tests as diagnostic tools. They showed clinical improvement after two weeks of valganciclovir therapy. Other organs' involvement was considered to be evaluated, including brain-evoked response audiometry (BERA) and eye examination. The physician should consider the possibility of CMV pneumonitis, who did not respond to standard and escalation of antibiotics treatment after initial diagnoses of bronchopneumonia.

The Influence of Herpes Family Viruses on the Course of Novel Coronavirus Infection

We have analyzed the impact of herpes virus infection on the course of a new coronavirus infection (NCVI). Infection of the examined contingent with herpes family viruses reached 95.3-100%. An association of NCVI with herpes simplex viruses 1, 2 types (HSV 1, 2 types) was found, but no correlation was found between the positivity coefficient (CP) of HSV 1, type 2 and the severity of NCVI. This can be explained by the fact that the sampling was carried out in the remote period after the transferred NKVI. Considering that both herpes viruses and the SARS-CoV-2 virus cause multiple organ damage and can aggravate each other, the study of co-infection seems to be very relevant.

Cytomegalovirus reactivation in patients diagnosed with severe COVID-19: A point prevalence study in a general hospital.

OBJECTIVE: To determine the prevalence of CMV reactivation in a population admitted for severe COVID-19 to a general hospital. METHODS: Point prevalence study in all hospitalized patients with severe COVID-19 (admitted either to general wards or ICU). Determination of the presence of CMV DNA in circulating blood. COVID-19 was confirmed in patients with compatible clinical manifestations, usually with pneumonia and a positive nasopharyngeal PCR test. RESULTS: We included 140 hospitalized patients with COVID-19 who consented to participate. A total of 16 patients (11.42%), had circulating CMV-DNA in peripheral blood at the time of the study. Patients with positive CMV viral load were mainly ICU patients (11/37 -29,7%) and only 5/103 cases (4,85%) were hospitalized into general wards. The accumulated doses of corticosteroids (prednisone equivalents) in the study day were (median and IQR) 987.50 mg (396.87-2,454.68) and 187.50 mg (75.00-818.12) respectively in CMV positive and negative patients (p < 0.001). A significant proportion of CMV positive patients were discovered because of the study and were clinically unsuspected by their physicians. The coinfected COVID-CMV positive population had a higher risk of accumulated secondary nosocomially-acquired infections and a worse prognosis. CONCLUSIONS: CMV reactivation should be systematically searched in patients in COVID-19 cases admitted to the ICU.

Correlation between severe acute respiratory syndrome Coronavirus-2 and cytomegalovirus

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), which causes the novel betacoronavirus 2019 disease (COVID-19), has become the first global pandemic in 100 years. Cytomegalovirus (CMV) is a prevalent herpesvirus that affects 40%-70% of the general population. This study aimed to see how CMV affected the presentation of COVID-19 infections as a prospective risk factor. Material and Methods: This study was conducted in Babylon, Iraq, from January to March, 2022. A total of 120 people were engaged in this study divided into four groups: mild, moderate, severe, and control group, 30 individuals in each group. Ninety patients identified with SARS-CoV-2 by PCR testing and 30 people serving as a control group. IgG antibody titer in blood samples were detected by mini vidas biomerieux. The samples were processed with the complete blood count (CBC) and ABO blood group. Independent T and Chi-square tests were used to examine the data using SPSS 21 software. Results: COVID-19 infection was more frequent in females than males. The COVID-19 patients were detected to have increased white blood cell count (p < 0.0001) and decreased lymphocytes compared to the healthy persons (p < 0.0001). No significant correlation between CMV and COVID-19 was discovered. CMV titer was not associated with disease severity. Blood group A is the most predominant type in patients compared to healthy persons. Conclusion: This study revealed no significant correlation between the severity of COVID-19 and CMV in spite of slightly increased in severe patients at mean 66.53 compared to the control group 58.80 (p = 0.26). Reactivation of CMV in COVID-19 patients may be associated with complications, so more attention should be taken into consideration regarding this virus, especially in severe patients. © 2022 Medical Journal of Dr. D.Y. Patil Vidyapeeth ;Published by Wolters Kluwer - Medknow.

MiniVent: A low-cost pressure-controlled ventilator system for emergency use

Objective: To address the issue of ventilator shortages due to the COVID-19 pandemic, our group developed the proof-of-concept of a low-cost and rapidly scalable open-source mechanical ventilator system for emergency use. Method(s): A simplified architecture of MiniVent was designed to meet the low-cost and easy-to-produce pre-established properties of our device. To carry out such an approach, we decided to use only components commonly available in the market or components of easy production with usual manufacturing techniques, such as 3D printing. The design of MiniVent comprises a pneumatic unit that controls the quality of the air and oxygen mixture and maintains the pressure on the patient's lungs at the desired preset value, along the respiratory cycle. The control unit was programmed on a microcontroller and is responsible for ensuring the respiratory rate and the inspiratory-expiratory ratio, selected by the user. To ensure the fulfilment of all the security and specification requirements of pandemic ventilators, we followed the mandatory specifications presented in the document - Rapidly Manufactured Ventilator System (RMVS) - published by the Medicines & Healthcare products Regulatory Agency (MHRA). A set of tests was performed using different ventilatory parameters for instrumental verification of MiniVent's physical and biological performance. A stability test was also carried out during 35 hours of uninterrupted operation to analyse whether the expected dynamics of the output pressure were maintained over this time. Result(s): The ventilator system developed allows prescribing different breathing rates, fractions inspired of oxygen (FiO2), inspiratory-expiratory ratios (I: E), positive inspiratory pressures (PIP) and positive end-expiratory pressures (PEEP), which can be easily adjustable to the patient's condition. The results of a set of tests assured the reliability of all the ventilatory parameters set by the user. Furthermore, MiniVent showed a good performance over 35 hours of uninterrupted operation, which pointed out the stability of this device. In addition, the device was tested in a porcine model showing good mechanical performance and adequate arterial blood gas throughout all test periods. When compared with commercial ventilators, MiniVent exhibited a similar performance of ventilation. Conclusion(s): MiniVent could be a reliable solution to overcome the shortage of commercial ventilators in emergencies, such as the recent COVID-19 pandemic. This device presents a production cost of under 1000 and does not need specialized technical assistance so it might be a viable solution even in lowerincome countries.

CXCL8, CCL2, and CMV Seropositivity as New Prognostic Factors for a Severe COVID-19 Course.

The exact pathophysiology of severe COVID-19 is not entirely elucidated, but it has been established that hyperinflammatory responses and cytokine storms play important roles. The aim of this study was to examine CMV status, select chemokines, and complement components in COVID-19, and how concentrations of given molecules differ over time at both molecular and proteomic levels. A total of 210 COVID-19 patients (50 ICU and 160 non-ICU patients) and 80 healthy controls were enrolled in this study. Concentrations of select chemokines (CXCL8, CXCL10, CCL2, CCL3, CCR1) and complement factors (C2, C9, CFD, C4BPA, C5AR1, CR1) were examined at mRNA and protein levels with regard to a COVID-19 course (ICU vs. non-ICU group) and CMV status at different time intervals. We detected several significant differences in chemokines and complement profiles between ICU and non-ICU groups. Pro-inflammatory chemokines and the complement system appeared to greatly contribute to the pathogenesis and development of severe COVID-19. Higher concentrations of CXCL8 and CCL2 in the plasma, with reduced mRNA expression presumably through negative feedback mechanisms, as well as CMV-positive status, correlated with more severe courses of COVID-19. Therefore, CXCL8, CCL2, and CMV seropositivity should be considered as new prognostic factors for severe COVID-19 courses. However, more in-depth research is needed.

Cytomegalovirus Proctitis Developed after COVID-19 Vaccine: A Case Report and Literature Review.

(1) Background: We describe a case of a 58-year-old Chinese woman, without obvious cause of immunosuppression, who developed cytomegalovirus (CMV) proctitis three days after a second COVID-19 vaccination. Electronic colonoscopy revealed a new lesion that was circumferential at the anorectal junction, with an uneven surface and ulceration, which mimicked rectal carcinoma. This is the first case of CMV proctitis following vaccination since the invention of the COVID-19 vaccine, suggesting that the COVID-19 vaccine may cause disorders of immune homeostasis, including not only immune hyperactivity but also immune deficiency. We report this case to increase readers' awareness of the risks after COVID-19 vaccination and to provide new ideas for the diagnosis and treatment of similar cases. (2) Methods: In this case, we used laboratory biochemical examinations, colonoscopy, immunohistochemistry, and a biochemical index to confirm the existence of CMV proctitis. (3) Results: In this case, the vaccine-induced CMV proctitis had a similar endoscopic appearance to rectal neoplastic lesions, which could be confirmed by biopsy and quickly relieved by ganciclovir treatment. Ganciclovir was used to treat the patient, and a good effect was observed. (4) Conclusions: COVID-19 vaccination may cause immune disorders, not just immune hyperactivity as previously reported, but also immune deficiency, such as CMV proctitis in this case. The clinical course of CMV proctitis secondary to COVID-19 vaccination was favorable with ganciclovir therapy.

A DNA-based non-infectious replicon system to study SARS-CoV-2 RNA synthesis.

The coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health around the world. In-depth studies on the pathogenic mechanisms of SARS-CoV-2 is urgently necessary for pandemic prevention. However, most laboratory studies on SARS-CoV-2 have to be carried out in bio-safety level 3 (BSL-3) laboratories, greatly restricting the progress of relevant experiments. In this study, we used a bacterial artificial chromosome (BAC) method to assemble a SARS-CoV-2 replication and transcription system in Vero E6 cells without virion envelope formation, thus avoiding the risk of coronavirus exposure. Furthermore, an improved real-time quantitative reverse transcription PCR (RT-qPCR) approach was used to distinguish the replication of full-length replicon RNAs and transcription of subgenomic RNAs (sgRNAs). Using the SARS-CoV-2 replicon, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 facilitates the transcription of sgRNAs in the discontinuous synthesis process. Moreover, two high-frequency mutants of N protein, R203K and S194L, can obviously enhance the transcription level of the replicon, hinting that these mutations likely allow SARS-CoV-2 to spread and reproduce more quickly. In addition, remdesivir and chloroquine, two well-known drugs demonstrated to be effective against coronavirus in previous studies, also inhibited the transcription of our replicon, indicating the potential applications of this system in antiviral drug discovery. Overall, we developed a bio-safe and valuable replicon system of SARS-CoV-2 that is useful to study the mechanisms of viral RNA synthesis and has potential in novel antiviral drug screening.

High Monocyte Count Associated with Human Cytomegalovirus Replication In Vivo and Glucocorticoid Therapy May Be a Hallmark of Disease.

Cytomegalovirus (CMV) syndrome and infectious disease are defined as pathogen detection with appropriate clinical symptoms, but there are not pathognomonic signs of CMV disease. Although the prodrome of acute minor viral infections leukopenia (lymphopenia and neutropenia) is noted with onset of fever, followed by monocytosis, the role of monocytosis in CMV disease has not been described. Furthermore, under influence of corticosteroid therapy, CMV reactivation and monocytosis are described, but without a strict relationship with steroids dose. In the study, the monocyte level was investigated during the CMV infectious process. Regrettably, a non-selected group of 160 patients with high CMV viremia showed high dispersion of monocyte level and comparable with the median value for healthy subjects. Therefore, we investigated monocyte level in CMV-infected patients in relation to the logarithmic phase of the infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. Significant monocytosis (above 1200/µL) during the logarithmic phase of CMV infection (with exponent between 3.23 and 5.77) was observed. Increased count and percentage of monocytes correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, glucocorticoids equivalent to 10 and 20 mg of dexamethasone during a 2-3-week period caused monocytosis-significant increase (to 1604 and 2214/µL, respectively). Conclusion: In light of the logarithmic increase of viral load, high monocytosis is a hallmark of CMV replication. In the COVID-19 era, presence of high virus level, especially part of virome (CMV) in the molecular technique, is not sufficient for the definition of either proven or probable CMV replication at any site. These preliminary observations merit additional studies to establish whether this clinical response is mediated by monocyte production or by decrease of differentiation to macrophages.

From Fetal to Neonatal Neuroimaging in TORCH Infections: A Pictorial Review.

Congenital infections represent a challenging and varied clinical scenario in which the brain is frequently involved. Therefore, fetal and neonatal neuro-imaging plays a pivotal role in reaching an accurate diagnosis and in predicting the clinical outcome. Congenital brain infections are characterized by various clinical manifestations, ranging from nearly asymptomatic diseases to syndromic disorders, often associated with severe neurological symptoms. Brain damage results from the complex interaction among the infectious agent, its specific cellular tropism, and the stage of development of the central nervous system at the time of the maternal infection. Therefore, neuroradiological findings vary widely and are the result of complex events. An early detection is essential to establishing a proper diagnosis and prognosis, and to guarantee an optimal and prompt therapeutic perinatal management. Recently, emerging infective agents (i.e., Zika virus and SARS-CoV2) have been related to possible pre- and perinatal brain damage, thus expanding the spectrum of congenital brain infections. The purpose of this pictorial review is to provide an overview of the current knowledge on fetal and neonatal brain neuroimaging patterns in congenital brain infections used in clinical practice.

Co-infection of Klebsiella pneumonia, Cytomegalovirus, Aspergillus and Zygomycete in a patient with SARS-CoV-2.

Co-infection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens has become a serious threat. There are the reports of fungal, bacterial, and viral co-infections with SARS-CoV-2. We report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia, and also klebsiella pneumoniae empyema as the complication of SARS-CoV-2.