Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the development of a new coronavirus disease (COVID-19), is a highly transmittable virus which, in just ten months, infected more than 40 million people in 214 countries worldwide. After inhalation, aerosols containing SARS-CoV-2 penetrate to the depths of the lungs and cause severe pneumonia, alveolar injury, and life-threatening acute respiratory distress syndrome (ARDS). Since there are no specific drugs or vaccines available to cure or prevent COVID-19 infection and COVID-19-related ARDS, a new therapeutic agent which will support oxygen supply and, at the same time, efficiently alleviate SARS-CoV-2-induced lung inflammation is urgently needed. Due to their potent immuno- and angiomodulatory characteristics, mesenchymal stem cells (MSCs) may increase oxygen supply in the lungs and may efficiently alleviate ongoing lung inflammation, including SARS-CoV-2-induced ARDS. In this review article, we described molecular mechanisms that are responsible for MSC-based modulation of immune cells which play a pathogenic role in the development of SARS-CoV-2-induced ARDS and we provided a brief outline of already conducted and ongoing clinical studies that increase our understanding about the therapeutic potential of MSCs and their secretome in the therapy of COVID-19-related ARDS.

Mesenchymal stem cells (MSCs) are adult, immunomodulatory stem cells which reside in almost all postnatal tissues. Viral antigens and damage-associated molecular patterns released from injured and infected cells activate MSCs, which elicit strong antiviral immune response. MSC-sourced interferons and inflammatory cytokines modulate the cytotoxicity of NK cells and CTLs, enhance the antigen-presentation properties of DCs and macrophages, regulate cytokine synthesis in CD4+ T helper cells and promote antibody production in B cells. After the elimination of viral pathogens, MSCs produce immunoregulatory cytokines and trophic factors, prevent the over-activation of immune cells and promote tissue repair and regeneration. In this review article, we summarize the current knowledge on the molecular mechanisms that are responsible for the MSC-dependent elimination of virus-infected cells, and we emphasize the therapeutic potential of MSCs and their secretomes in the treatment of viral diseases.

Hepatitis C virus infection (HCV), one of the greatest causes of liver disease, is a frequent complication in patients with end-stage renal disease (ESRD) on dialysis. ESRD is defined as decreased glomerular filtration and also accompanied by impaired function of the immune system. Galectin-3 is aβ-galactoside-binding lectin, involved in various biological processes including pathogenesis of chronic renal disease. The aim of our study was to estimate disease severity in ESRD HCV⁺patients and analyze the serum concentrations of IL-1β, IL-4, IL-23, and IL-6; anti-HCV antibodies; and galectin-3. Also, we attempted to determine potential correlation between galectin-3 level and parameters of disease severity ALT and AST. Our results showed decreased levels of ALT and AST (p=0.00), demonstrating less liver destruction in ESRD HCV⁺patients in comparison to HCV⁺patients. Increased levels of IL-6 (p=0.03) implicate a hepatoprotective role of IL-6 in these patients. Also, level of galectin-3 (p=0.00) in the serum of ESRD HCV⁺patients was higher than that of HCV⁺patients. This alteration was accompanied with negative correlation between galectin-3 and AST and ALT, respectively (p=0.029;p=0.033). The presence of increased systemic levels of IL-6 and Gal-3 in ESRD HCV⁺patients may be an attempt to counteract or limit ongoing proinflammatory processes and to downregulate chronic inflammation, suggesting the new aspects of HCV infection in ESRD patients.

Background/Aim. The differential diagnosis of fever of unknown origin (FUO) includes more than 200 different diseases and conditions. The aim of this study was to identify the most frequent causes of FUO among adult patients according to gender and age. Methods. The study included 74 patients examined from June 2010 to June 2013 at the Infectious Disease Clinic, Clinical Center Kragujevac in Serbia, according to the defined criteria for FUO. The patients were divided according to the diagnosis into four groups: infectious, malignant, rheumatic and "other diseases". A cause of febricity could not be estabilshed in a portion of subjects, and they comprised the group of undiagnosed cases. Results. Infectious diseases were dominant in the study, followed by rheumatic diseases, which were most frequently found in women and the elderly. The diseases recognised as the most common causes of febricity were subacute thyroiditis, subacute endocarditis, Still?s disease, rheumatic polymyalgia with or without temporal arteritis, and cytomegalovirus infection. In 44% of the patients, the final diagnosis was composed of only six clinical entities. Conclusion. The importance of establishing the diagnosis of rheumatic disease is especially emphasised, in line with other authors? research indicating the number of these diseases is on the rise. The diagnostic approach to FUO should always be directed to the known frequency of diseases.

SARS-CoV-2 continues to pose a major challenge to scientists and clinicians. We examined the significance of the serum concentrations of vitamin D, albumin, and D-dimer for the severity of the clinical picture and mortality in COVID-19. Materials and methods: A total of 288 patients treated for COVID-19 infection participated in the research. The patients were treated in the period from May 2020 to January 2021. All patients were divided based on the need for oxygen therapy (Sat > 94%) into patients with mild or severe clinical pictures. The biochemical and radiographic parameters of the patients were analyzed. Appropriate statistical methods were used in the statistical analysis. Results: In patients with COVID-19 with confirmed severe clinical pictures, lower values of serum albumin (p < 0.0005) and vitamin D (p = 0.004) were recorded, as opposed to elevated values of D-dimer (p < 0.0005). Accordingly, the patients with fatal disease outcomes had lower levels of albumin (p < 0.0005) and vitamin D (p = 0.002), while their D-dimer (p < 0.0005) levels were elevated. An increase in the radiographic score, as a parameter for assessing the severity of the clinical picture, was accompanied by a decrease in serum albumin (p < 0.0005) and a simultaneous increase in D-dimer (p < 0.0005), without a change in the vitamin D concentration (p = 0.261). We also demonstrated the interrelations of the serum levels of vitamin D, albumin, and D-dimer in patients with COVID-19 as well as their significance as predictors of the outcome of the disease. Conclusion: The significance of the predictive parameters in our study indicates the existence of an important combined role of vitamin D, albumin, and D-dimer in the early diagnosis of the most severe patients suffering from COVID-19. Reduced values of vitamin D and albumin, in combination with elevated values of D-dimer, can be timely indicators of the development of a severe clinical picture and death due to COVID-19.

Background/Aim. COVID 19 is a predominantly respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to determine whether there are significant variables which could predict severe clinical picture and fatal outcome in COVID 19 patients. Methods. The research involved 632 patients who were treated at the University Medical Center Kragujevac at the Clinic for Infectious Diseases, in the period from June 2020 to February 2021. All patients were divided into two groups according to the need for oxygen therapy (Sat 02 < 94. Results. Our results showed that high BMI was singled out as a risk factor for the development of a severe clinical picture [BMI [ORadjusted = 1.263; 95% CI = 1.117 - 1.427; p < 0.001]]. Prothrombin time (ORadjusted = 1.170; 95% CI = 1.004 - 1.364; p = 0.045), as well as low albumin values (ORadjusted = 0.878; 95% CI = 0.804 - 0.958; p = 0,003) had a predictive significance for the development of severe clinical picture. Factors that were of predictive importance in patients with fatal outcome were CRP (ORadjusted = 1.010; 95% CI = 1.001 - 1.019; p = 0.031), LDH (ORadjusted = 1.004; 95% CI = 1.001 - 1.006; p = 0.002). X-ray of the lungs (ORadjusted = 1.394; 95% CI = 1.170 - 1.661; p < 0.001). Conclusion. Research has shown that routine, clinical-laboratory parameters can be important in the early detection of patients with a potentially severe clinical picture and fatal outcome. In patients with a mild clinical picture, CRP, LDH, ferritin, and serum albumin levels may indicate timely disease progression. Monitoring of parameters of essential importance for the timely clinical assessment of patients with COVID 19, and thus the timely application of adequate therapeutic protocols in the treatment of these patients.