Cytomegalovirus, a "Friend" of SARS-CoV-2: A Case Report.

INTRODUCTION: Cytomegalovirus (CMV) infection is present in a latent state in 70-90% of the immunocompetent population, and its reactivation might be triggered by inflammatory conditions such as post-COVID multisystem inflammatory syndrome (MIS-C) or by immunosuppression induced by steroids. The aim of this paper was to highlight the unexpected complications associated with SARS-CoV-2 infection that require a complex clinical approach for accurate diagnosis. MATERIALS AND METHODS: We present the case of a 4-year-old male patient who, during an initially favorable course of PIMS, experienced symptoms of respiratory failure. RESULTS: The patient initially presented with clinical and paraclinical signs of PIMS with cardiac involvement, for which high-dose corticosteroid therapy was initiated, followed by gradual tapering, along with immunoglobulins, anticoagulants, antiplatelet agents, and symptomatic treatment. After 10 days of favorable progress, the patient's general condition deteriorated, showing tachypnea, desaturation, and a ground-glass appearance on thoracic CT. Negative inflammatory markers and favorable cardiac lesion evolution ruled out MIS-C relapse. The presence of anti-CMV IgM antibodies and viral DNA in the blood confirmed acute CMV infection, likely triggered by prior severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) infection and secondary immunosuppression due to steroids. Non-specific immunomodulatory treatment was initiated but led to worsening of pulmonary lesions, prompting the initiation of specific antiviral treatment with ganciclovir, resulting in rapid clinical and imaging improvement. CONCLUSIONS: CMV infection can be reactivated by immunosuppression induced by corticosteroid therapy for MIS-C and may require specific etiological treatment.

The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis.

Background and Objectives: Sepsis involves a dysregulated host response, characterized by simultaneous immunosuppression and hyperinflammation. Initially, there is the release of pro-inflammatory factors and immune system dysfunction, followed by persistent immune paralysis leading to apoptosis. This study investigates sepsis-induced apoptosis and its pathways, by assessing changes in PD-1 and PD-L1 serum levels, CD4+ and CD8+ T cells, and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) severity scores. Materials and Methods: This prospective, observational, single-centre study enrolled 87 sepsis patients admitted to the intensive care unit at the County Emergency Clinical Hospital in Târgu Mureș, Romania. We monitored the parameters on day 1 (the day sepsis or septic shock was diagnosed as per the Sepsis-3 Consensus) and day 5. Results: Our study found a statistically significant variation in the SOFA score for the entirety of the patients between the studied days (p = 0.001), as well as for the studied patient groups: sepsis, septic shock, survivors, and non-survivors (p = 0.001, p = 0.003, p = 0.01, p = 0.03). On day 1, we found statistically significant correlations between CD8+ cells and PD-1 (p = 0.02) and PD-L1 (p = 0.04), CD4+ and CD8+ cells (p < 0.0001), SOFA and APACHE II scores (p < 0.0001), and SOFA and APACHE II scores and PD-L1 (p = 0.001 and p = 0.01). On day 5, we found statistically significant correlations between CD4+ and CD8+ cells and PD-L1 (p = 0.03 and p = 0.0099), CD4+ and CD8+ cells (p < 0.0001), and SOFA and APACHE II scores (p < 0.0001). Conclusions: The reduction in Th CD4+ and Tc CD8+ lymphocyte subpopulations were evident from day 1, indicating that apoptosis is a crucial factor in the progression of sepsis and septic shock. The increased expression of the PD-1/PD-L1 axis impairs costimulatory signalling, leading to diminished T cell responses and lymphopenia, thereby increasing the susceptibility to nosocomial infections.

The Prognostic Utility of Cytokines in Hospitalized COVID-19 Patients.

Introduction: The severity of COVID-19 relies on several factors, but the overproduction of pro-inflammatory cytokines remains a central mechanism. The aim of this study was to investigate the predictive utility of interleukin (IL)-6, IL-8, IL-10, IL-12, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) measurement in patients with COVID-19. Material and Methods: We prospectively enrolled 181 adult patients with COVID-19 admitted to the 1st Infectious Disease County Hospital Târgu Mureș from December 2020 to September 2021. Serum cytokine levels were measured and correlated with disease severity, need for oxygen therapy, intensive care unit (ICU) transfer, and outcome. Results: We found significantly higher serum levels of IL-6, IL-8, and IL-10 in patients with severe COVID-19 and in those with a fatal outcome. The logistic regression analysis showed a significant predictive value for IL-8 regarding disease severity, and for IL6 and IL-10 regarding ICU transfer and fatal outcome. Conclusions: Serum levels of IL-6, IL-8, and IL-10 were significantly increased in patients with COVID-19, but their predictive value regarding disease severity and the need for oxygen therapy was poor. We found IL-6 and IL-10 to have a good predictive performance regarding ICU transfer and fatal outcome.

Is Carboxyhaemoglobin an Effective Bedside Prognostic Tool for Sepsis and Septic Shock Patients?

Introduction: Proper management of sepsis poses a challenge even today, with early diagnosis and targeted treatment being the most important steps. Easy, cost-effective bedside tools are needed in order to pinpoint towards the outcome of sepsis or septic shock. Aim of study: This study aims to find a correlation between Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) severity scores, the Neutrophil-Lymphocytes Ratio (NLR) and carboxyhaemoglobin (COHb) levels in septic or septic shock patients with the scope of establishing a bed side cost-effective prognostic tool. Materials and methods: A pilot, prospective, observational, and ongoing study was conducted on 61 patients admitted with sepsis or septic shock according to the SEPSIS 3 Consensus definition. We followed clinical and paraclinical parameters on day 1 (D1) and day 5 (D5) after meeting the inclusion criteria. Results: On D1 we found a statistically significant positive correlation between each severity score (p <0.0001), r = 0.7287 for SOFA vs. APACHE II with CI: 0.5841-0.8285, r = 0.6862 for SOFA vs. SAPS II with CI: 0.5251-0.7998 and r = 0.8534 for APACHE II vs. SAPS II with CI: 0.7663 to 0.9097. On D5 we observed similar results: a significant positive correlation between each severity score (p <0.0001), with r = 0.7877 for SOFA vs. APACHE II with CI: 0.6283 to 0.8836, r = 0.8210 for SOFA vs. SAPS II with CI: 0.6822 to 0.9027 and r = 0.8880 for APACHE II vs. SAPS II., CI: 0.7952 to 0.9401. Nil correlation was found between the severity scores, NLR and COHb on D1 and D5. Conclusion: Cost-effective bedside tools to pinpoint towards the outcome of sepsis are yet to be found, however the positive correlation between the severity scores point out to a combination of such tools for prognosis prediction of septic or septic shock patients.

The Crosstalk between Vitamin D and Pediatric Digestive Disorders.

Vitamin D is a cyclopentane polyhydrophenanthrene compound involved mainly in bone health and calcium metabolism but also autophagy, modulation of the gut microbiota, cell proliferation, immune functions and intestinal barrier integrity. The sources of vitamin D include sunlight, diet and vitamin D supplements. Vitamin D3, the most effective vitamin D isoform is produced in the human epidermis as a result of sunlight exposure. Vitamin D undergoes two hydroxylation reactions in the liver and kidney to reach its active form, 1,25-dihydroxyvitamin D. Recent studies highlighted a complex spectrum of roles regarding the wellbeing of the gastrointestinal tract. Based on its antimicrobial effect, it was recently indicated that vitamin D supplementation in addition to standard eradication therapy might enhance H. pylori eradication rates. Moreover, it was suggested that low levels of vitamin D might also be involved in the acquisition of H. pylori infection. In terms of celiac disease, the negative effects of vitamin D deficiency might begin even during intrauterine life in the setting of maternal deficiency. Moreover, vitamin D is strongly related to the integrity of the gut barrier, which represents the core of the pathophysiology of celiac disease onset, in addition to being correlated with the histological findings of disease severity. The relationship between vitamin D and cystic fibrosis is supported by the involvement of this micronutrient in preserving lung function by clearing airway inflammation and preventing pathogen airway colonization. Moreover, this micronutrient might exert anticatabolic effects in CF patients. Inflammatory bowel disease patients also experience major benefits if they have a sufficient level of circulating vitamin D, proving its involvement in both induction and remission in these patients. The findings regarding the relationship between vitamin D, food allergies, diarrhea and constipation remain controversial, but vitamin D levels should be monitored in these patients in order to avoid hypo- and hypervitaminosis. Further studies are required to fill the remaining gaps in term of the complex impact of vitamin D on gastrointestinal homeostasis.

Dynamic Evaluation of Natural Killer Cells Subpopulations in COVID-19 Patients.

The aim of the study was to evaluate the dynamic changes of the total Natural Killer (NK) cells and different NK subpopulations according to their differentiated expression of CD16/CD56 in COVID-19 patients. Blood samples with EDTA were analyzed on day 1 (admission moment), day 5, and day 10 for the NK subtypes. At least 30,000 singlets were collected for each sample and white blood cells were gated in CD45/SSC and CD16/CD56 dot plots of fresh human blood. From the lymphocyte singlets, the NK cells subpopulations were analyzed based on the differentiated expression of surface markers and classified as follows: CD16-CD56+/++/CD16+CD56++/CD16+CD56+/CD16++CD56-. By examining the CD56 versus CD16 flow cytometry dot plots, we found four distinct NK sub-populations. These NK subtypes correspond to different NK phenotypes from secretory to cytolytic ones. There was no difference between total NK percentage of different disease forms. However, the total numbers decreased significantly both in survivors and non-survivors. Additionally, for the CD16-CD56+/++ phenotype, we observed different patterns, gradually decreasing in survivors and gradually increasing in those with fatal outcomes. Despite no difference in the proportion of the CD16-CD56++ NK cells in survivors vs. non-survivors, the main cytokine producers gradually decline during the study period in the survival group, underling the importance of adequate IFN production during the early stage of SARS-CoV-2 infection. Persistency in the circulation of CD56++ NK cells may have prognostic value in patients, with a fatal outcome. Total NK cells and the CD16+CD56+ NK subtypes exhibit significant decreasing trends across the moments for both survivors and non-survivors.

COVID-19 and PIMS-Two Different Entities, but the Same Trigger.

COVID-19 and PIMS represent two novel pathologies that have challenged the medical world during the last two years on account of their being very similar, but yet very different. Our aim was to comparatively assess children with SARS-CoV-2 infection and PIMS in terms of symptoms, clinical findings, laboratory parameters, echocardiography, and evolution. Our retrospective study included 46 children with COVID-19 (group 1), and 20 children with confirmed PIMS (group 2). We found no significant differences in terms of age, gender, and originating area between the two groups. We noticed that fever was significantly more common in the PIMS group as compared to COVID-19 group (p = 0.0217). In terms of laboratory parameters, increased bilirubin and creatinine were significantly more frequent in children with COVID-19 (p = 0.0064/p = 0.0064), while hypoalbuminemia and elevated ESR were significantly more common in those with PIMS (p < 0.0001/p = 0.0127). Moreover, prognosis parameters such as D-dimers, NT-proBNP, and CK-MB were also found to be significantly higher in the PIMS group as compared to COVID-19 group (p = 0.0003/p = 0.0182/p = 0.0007). In terms of complications, most were identified in PIMS group, among which cardiac and liver impairment along with dehydration were significantly more common in children diagnosed with PIMS as compared to those detected with COVID-19. Similarly, children with PIMS had a significantly higher chance to have pathological echocardiography changes. Although difficult, the distinction between COVID-19 and PIMS is crucial for the patient's long-term outcome.