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.

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.

Reply to Chambers, P. Comment on "Huțanu et al. Low Serum Vitamin D in COVID-19 Patients Is Not Related to Inflammatory Markers and Patients' Outcomes-A Single-Center Experience and a Brief Review of the Literature. Nutrients 2022, 14, 1998".

We thank Patrick Chambers for his interest [...].

Low Serum Vitamin D in COVID-19 Patients Is Not Related to Inflammatory Markers and Patients' Outcomes-A Single-Center Experience and a Brief Review of the Literature.

The aim of the study was to evaluate the vitamin D status in hospitalized COVID-19 patients and the correlation with C reactive protein (CRP), ferritin, fibrinogen, and peripheral blood leukocytes, as well as inflammatory derived indices. A prospective study was performed on 203 COVID-19 hospitalized patients, classified by disease severity. Blood was collected after admission, and inflammatory biomarkers and vitamin D status were assessed using routine laboratory procedures. No significant correlation was found between vitamin D serum levels and disease severity stratified by different age groups. However, the highest vitamin D levels were found in patients with mild disease: median 29.39 (IQR 12.12-44.02) ng/mL, while for moderate and severe forms the serum levels were significantly lower: median 15.10 (IQR 9.56-24.11) ng/mL for moderate, and 18.86 (IQR 12.50-27.88) ng/mL for severe; p = 0.009. Patients with no comorbidities showed a significantly higher level of vitamin D median 24.72 (IQR 16.05-31.52) ng/mL compared to subjects with at least one comorbidity: median 16.02 (IQR 9.81-25.22) ng/mL, p = 0.004. We did not find an association between vitamin D levels and inflammatory biomarkers except for significantly lower vitamin D levels in moderate and severe COVID-19 compared to mild disease forms.