Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin–angiotensin–aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients.

Acute hyperglycaemia is a common COVID-19 complication linked to adverse outcomes. The combined prognostic value of cytokine activation and acute insulin resistance in non-diabetic patients remains unclear. In this prospective cohort study, we enrolled 144 hospitalised adults with RT-PCR-confirmed SARS-CoV-2 infection and no prior diabetes. We aimed to characterise metabolic–inflammatory phenotypes and evaluate their association with disease severity and post-discharge glycaemic outcomes. Patients were classified as normoglycaemic or dysglycaemic based on repeated glucose profiles. Dysglycaemic patients were further phenotyped as stress hyperglycaemia (SHG) or newly diagnosed diabetes (NOD). This classification was based on post-discharge glycaemic assessment at 3 and 6 months, distinguishing transient from persistent hyperglycaemia. Admission hyperglycaemia was associated with a consistently elevated pro-inflammatory cytokine pattern. However, cytokine concentrations were comparable between stress hyperglycaemia and newly diagnosed diabetes, indicating that inflammatory burden alone does not explain metabolic persistence. In contrast, insulin resistance (HOMA-IR) was markedly higher in the newly diagnosed diabetes phenotype. Along with admission oxygenation and key cytokine signals, this contributed to risk stratification for severe disease. In conclusion, early admission assessment of glucose and insulin resistance identifies high-risk metabolic phenotypes. This enables targeted in-hospital risk stratification and post-discharge glycaemic surveillance.

Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study. Reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect flavivirus RNA in clinical samples (cerebrospinal fluid; CSF, urine). ELISA was used for IgM and IgG antibody detection in serum and CSF with confirmation of cross-reactive samples by virus neutralization test. WNV was detected more frequently (74.4%) than TBEV (25.6%). A statistically significant age difference was found between WNV patients (median 65 years) and TBEV patients (median 36 years). Comorbidities were more frequently detected in WNV patients (hypertension 56.3 vs. 18.2%; diabetes 31.3 vs. 0%). Meningitis was the most common clinical presentation in both TBE and WNV neuroinvasive disease (WNND; 63.6 and 59.4%, respectively). In addition, some rare clinical presentations of WNND were also detected (cerebellitis, polyradiculoneuritis). No significant differences in the frequency of clinical symptoms were observed between WNV and TBEV-infected patients (fever 93.7 vs. 100%; malaise 78.1 vs. 100%; headache 75.0 vs. 100%; nausea 50.0 vs. 63.6%; vomiting 34.4 vs. 54.6%). Comparative analysis of total and differential leukocyte blood count showed similar results. However, CSF pleocytosis was higher in TBE patients, with a significant difference in the neutrophil and lymphocyte count (WNND median 48.5% and 51.5%; TBE median 10.0 and 90.0%, respectively). The length of hospital stay was 12 days for WNND and 9 days for TBE. Phylogenetic analysis of detected WNV strains revealed the presence of WNV lineage 2 in eastern Croatia.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein secreted by activated neutrophils and certain tissues. The aim of this study was to investigate the prognostic role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in hospitalized COVID-19 patients with regard to mortality. The prospective observational cohort study involved 86 hospitalized adult COVID-19 patients. Patients’ urine samples were collected upon admission and 48–72 h after admission. General anamnesis and clinical status information were obtained from medical records. Within 24 h of sample collection, urine aliquots were centrifuged, the supernatant was separated, and samples were frozen at −80 °C until uNGAL concentration measurement, which was performed within two years of sample collection. The patients were categorized into groups based on disease outcome (survived/deceased). Data analysis was performed to identify predictive factors and diagnostic indicators for the unfavorable outcome group using logistic regression and ROC curve methods. Logistic regression associated age, cardiomyopathy, invasive mechanical ventilation, and uNGAL concentration (follow-up sampling) with mortality. ROC analysis identified uNGAL concentration (follow-up sampling) as an indicator of mortality, with a cut-off value of >23.8 ng/mL. This study concludes that there is an association between disease outcome and uNGAL concentration in COVID-19 patients. However, understanding the dynamics of uNGAL concentration during COVID-19 remains limited, which is crucial for its effective clinical application.

Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine associated with acute and chronic inflammatory states. This prospective observational study aimed to investigate the prognostic roles of GDF-15 and routine clinical laboratory parameters in COVID-19 patients. Upon the admission of 95 adult hospitalized COVID-19 patients in Croatia, blood analysis was performed, and medical data were collected. The patients were categorized based on survival, ICU admission, and hospitalization duration. Logistic regression and ROC curve methods were employed for the statistical analysis. Logistic regression revealed two independent predictors of negative outcomes: CURB-65 score (OR = 2.55) and LDH (OR = 1.005); one predictor of ICU admission: LDH (OR = 1.004); and one predictor of prolonged hospitalization: the need for a high-flow nasal cannula (HFNC) upon admission (OR = 4.75). The ROC curve showed diagnostic indicators of negative outcomes: age, CURB-65 score, LDH, and GDF-15. The largest area under the curve (AUC = 0.767, specificity = 65.6, sensitivity = 83.9) was represented by GDF-15, with a cutoff value of 3528 pg/mL. For ICU admission, significant diagnostic indicators were LDH, CRP, and IL-6. Significant diagnostic indicators of prolonged hospitalization were CK, GGT, and oxygenation with an HFNC upon admission. This study reaffirms the significance of the commonly used laboratory parameters and clinical scores in evaluating COVID-19. Additionally, it introduces the potential for a new diagnostic approach and research concerning GDF-15 levels in this widespread disease.

Background: COVID-19 is a multisystem disorder associated with inflammatory, metabolic, electrolyte, and endocrine disturbances. However, the clinical relevance of dysnatremia and acute hormonal alterations remains uncertain, particularly when assessed alongside established clinical risk factors. Methods: This prospective cohort study included 252 adults hospitalized with confirmed COVID-19. Clinical, laboratory, hormonal, and metabolic parameters were assessed at admission, and their associations with disease severity, intensive care unit (ICU) admission, and in-hospital mortality were analyzed. Results: The median age was 73 years, 50.4% of patients were female, and severe or critical disease was present in 81.7%. Dysnatremia and/or endocrine alterations were detected in 55.2% of patients, including hyponatremia in 16.7%, while thyroid-function alterations were observed in 40.9%. Dysnatremia was associated with higher glucose levels and inflammatory-cell changes. Several hormonal and metabolic parameters showed statistically significant univariate associations with adverse outcomes; however, their discriminative performance was weak, with AUC values below clinically meaningful thresholds. After adjustment for major clinical confounders, dysnatremia and endocrine alterations were not independent predictors of disease severity, ICU admission, or mortality. Conclusions: These findings suggest that electrolyte and endocrine abnormalities in hospitalized COVID-19 patients primarily reflect systemic stress physiology and acute disease burden rather than functioning as independent prognostic biomarkers.