Calprotectin, a Promising Serological Biomarker for the Early Diagnosis of Superinfections with Multidrug-Resistant Bacteria in Patients with COVID-19.

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.

Minimally-invasive tracheostomy (MIT): A care bundle for safety improvement in high-risk critically ill patients.

BACKGROUND: Detailed reports are scarce on minimally-invasive tracheostomy (MIT) techniques for critically ill patients with challenging anatomy or complex coagulopathies. In such high-risk patients, conventional percutaneous dilatational tracheostomy (PDT) may lead to severe complications. METHODS: Aiming to broaden the scope of MIT for patients previously excluded due to high risks, we developed a new care bundle (MIT technique), specifically designed for intensive care specialists. Our study examined the outcomes of MIT in 32 high-risk patients treated in an ICU of a University Hospital with specific focus on gastrointestinal and liver diseases. RESULTS: We have modified the conventional PDT technique by incorporating an initial skin incision, blunt dissection, diaphanoscopy-guided probe puncture, and continuous bronchoscopic monitoring. Our care bundle also introduces an anterolateral approach for tracheal entry, a significant advancement for patients with complex neck anatomy or dense vasculature, where an anterolateral trajectory avoids midline blood vessels. This enhanced method has proven to be safer than traditional PDT, with a notable absence of post-procedural hemorrhages, cannula misplacements, or infections. CONCLUSION: The use of our refined care bundle enabled swift minimally-invasive tracheostomy in high-risk patients without the occurrence of serious complications.

Lipid Metabolism Disorders as Diagnostic Biosignatures in Sepsis.

Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in human sepsis. ApoA-IV (analyzed in 156 patients with systemic inflammatory response syndrome (SIRS)/sepsis) and cholesteryl ester (CE) (analyzed in 121 of these patients) were lower in patients compared to 43 healthy controls. In contrast, triglyceride (TG) levels were elevated in patients. ApoA-IV levels in plasma of the patients did not correlate with these lipids. Patients with SIRS, sepsis or septic shock had comparable apoA-IV, TG, CE and free cholesterol (FC) levels. Patients on dialysis had significantly lower CE levels, whereas apoA-IV levels did not change much. CE levels were elevated in patients with viral sepsis due to SARS-CoV-2 infection in comparison to SIRS/sepsis patients not infected by this virus. CE levels correlated negatively with procalcitonin, interleukin-6 and bilirubin, while TGs were positively associated with bilirubin and C-reactive protein. ApoA-IV, TG, CE and FC levels were not associated with bacterial infection or survival. In conclusion, this analysis suggests that CE levels decline in sepsis-related renal failure and also shows that plasma apoA-IV and CE levels are early biomarkers of sepsis.

Exploring the Thioredoxin System as a Therapeutic Target in Cancer: Mechanisms and Implications.

Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O2) is used for energy production, generating reactive oxygen species (ROS) as byproducts of enzymatic reactions. To protect against oxidative damage, cells possess an intricate system of redox scavengers and antioxidant enzymes, collectively forming the antioxidant defense system. This system maintains the redox equilibrium and enables the generation of localized oxidative signals that regulate essential cellular functions. One key component of this defense is the thioredoxin (Trx) system, which includes Trx, thioredoxin reductase (TrxR), and NADPH. The Trx system reverses oxidation of macromolecules and indirectly neutralizes ROS via peroxiredoxin (Prx). This dual function protects cells from damage accumulation and supports physiological cell signaling. However, the Trx system also shields tumors from oxidative damage, aiding their survival. Due to elevated ROS levels from their metabolism, tumors often rely on the Trx system. In addition, the Trx system regulates critical pathways such as proliferation and neoangiogenesis, which tumors exploit to enhance growth and optimize nutrient and oxygen supply. Consequently, the Trx system is a potential target for cancer therapy. The challenge lies in selectively targeting malignant cells without disrupting the redox equilibrium in healthy cells. The aim of this review article is threefold: first, to elucidate the function of the Trx system; second, to discuss the Trx system as a potential target for cancer therapies; and third, to present the possibilities for inhibiting key components of the Trx system, along with an overview of the latest clinical studies on these inhibitors.

Chemerin Levels in COVID-19 Are More Affected by Underlying Diseases than by the Virus Infection Itself.

BACKGROUND/OBJECTIVES: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association between serum chemerin levels and COVID-19 disease severity and outcomes has not been definitively established. METHODS: In this study, serum chemerin levels were analyzed in 64 patients with moderate COVID-19 and 60 patients with severe disease. RESULTS: The results showed that serum chemerin levels were comparable between these two groups and slightly higher than in healthy controls. Notably, COVID-19 patients with hypertension exhibited elevated serum chemerin levels, while those with liver cirrhosis had lower levels. When patients with these comorbidities were excluded from the analyses, serum chemerin levels in COVID-19 patients were similar to those in healthy controls. Positive correlations were observed between serum chemerin levels and markers such as alkaline phosphatase, C-reactive protein, eosinophils, and lymphocytes in the entire cohort, as well as in the subgroup excluding patients with hypertension and cirrhosis. Additionally, urinary chemerin levels were comparable between COVID-19 patients and controls, and neither hypertension nor dialysis significantly affected urinary chemerin levels. Both survivors and non-survivors had similar serum and urinary chemerin levels. CONCLUSIONS: In conclusion, this study suggests that comorbidities such as arterial hypertension and liver cirrhosis do have a more significant impact on serum chemerin levels than SARS-CoV-2 infection itself.

Leishmania donovani infection mimicking ulcerative colitis in an immuno-competent patient.

We share a case of a 54-year-old Caucasian immune-competent male with a suspected long latent visceral leishmaniasis presenting primarily with parasitic colitis, splenomegaly, and pancytopenia. Due to histopathologically and endoscopically mimicking ulcerative colitis, the patient was initially treated for UC, until the parasites were identified and eradicated with liposomal Amphotericin B.

Cost-effectiveness in an interprofessional training ward within a university department for internal medicine: a monocentric open-label controlled study of the A-STAR Regensburg.

Introduction: Interprofessional collaboration in healthcare involves diverse professionals working together to address complex patient needs. Interprofessional training wards offer workplace-based interprofessional education in real healthcare settings, fostering collaborative learning among students. While their educational value is widely recognized, debates persist regarding their cost-effectiveness due to limited research. This study assesses the cost efficiency of the interprofessional training ward Regensburg (A-STAR) within the Department of Internal Medicine I at the University Hospital Regensburg, compared to conventional wards. Methods: From October 2019 to December 2022, 7,244 patient cases were assigned to A-STAR or conventional wards by case managers, with a comprehensive analysis of all associated revenues and costs. Results: A-STAR treated 1,482 patients, whereas conventional wards treated 5,752 patients, with more males and younger patients at A-STAR. A-STAR achieved higher profit per case (€1,508.74) attributed to increased revenues and reduced material costs. It generated an average of €1,366.54 more Diagnosis Related Groups (DRG) revenue per case annually than conventional wards, due to greater medical complexity reflected in a higher case-mix index (CMI: 2.4 vs. 2.2). The increased case complexity led to longer patient stays (9.0 vs. 8.1 days) and fewer cases treated annually at A-STAR (27.4 cases/year vs. 37.8 cases/year). The higher CMI did not result in a higher proportion of patients requiring isolation. A-STAR exhibited a higher capacity utilization rate (87.1% vs. 83.9%). Personnel costs per case at A-STAR were initially elevated due to enhanced observation by the senior physician but were gradually mitigated by expanding A-STAR's bed capacity. Material costs were consistently lower on a per-case basis at A-STAR (€1512.02 vs. €1577.12), particularly in terms of medication expenses, indicating more resource-efficient operations. From the A-STAR graduates, 18 individuals were recruited for permanent positions as doctors or nurses over 2 years. Conclusion: A-STAR demonstrates economic efficiency and stability even during the COVID-19 pandemic. The substantial personnel acquisition is likely influenced by high levels of satisfaction with education and work and is economically relevant in medical staff shortages. These findings provide a compelling rationale for the broader implementation of interprofessional training wards, establishing them as vital platforms for nurturing future professionals.

Photodynamic coatings kill bacteria on near-patient surfaces in intensive care units with low light intensities.

BACKGROUND: Surfaces in close proximity to patients within hospitals may cause healthcare-associated infections. These surfaces are repositories for pathogens facilitating their transmission among staff and patients. Regular cleaning and disinfection of these surfaces provides only a temporary elimination of pathogens with inevitable recontamination. Antimicrobial coatings (AMC) of such surfaces may additionally reduce the risk of pathogen transmissions. The study aimed to find out whether photodynamic coatings can be effective even at very low light intensities. AIM: To evaluate the efficacy of a standard and a novel photodynamic AMC in a field study conducted in two ICUs at our university hospital. METHODS: The microbial burden was determined on three coatings: standard photodynamic AMC (A), a novel photodynamic AMC (B), and an inactive AMC as control (C). The control coating C was identical to standard coating A, but it contained no photosensitizer. During a 3-month period, 699 samples were collected from identical surfaces using eSwab and were analyzed (cfu/cm2). FINDINGS: Mean values of all surfaces covered with control coating (C) showed a microbial burden of 5.5 ± 14.8 cfu/cm2. Photodynamic AMC showed significantly lower mean value of 1.6 ± 4.6 CFU/cm2 (coating A; p<0.001) and 2.7 ± 9.6 (coating B; p<0.001). When considering a benchmark of 2.5 cfu/cm2, the relative risk for higher microbial counts was reduced by 52 % (coating A) or 40 % (coating B), respectively. CONCLUSIONS: Both photodynamic AMCs offer a substantial, permanent risk reduction of microbial counts on near patient surfaces in ICUs with low light intensities.

Reduced Plasma Bone Morphogenetic Protein 6 Levels in Sepsis and Septic Shock Patients.

Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6.

High Serum S100A12 as a Diagnostic and Prognostic Biomarker for Severity, Multidrug-Resistant Bacteria Superinfection and Herpes Simplex Virus Reactivation in COVID-19.

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.

Proprotein Convertase Subtilisin/Kexin Type 9 Induction in COVID-19 Is Poorly Associated with Disease Severity and Cholesterol Levels.

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19.

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis.

Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.

Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling.

Reactive oxygen species (ROS) are central to inter- and intracellular signaling. Their localized and transient effects are due to their short half-life, especially when generated in controlled amounts. Upon T cell receptor (TCR) activation, regulated ROS signaling is primarily initiated by complexes I and III of the electron transport chain (ETC). Subsequent ROS production triggers the activation of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2), prolonging the oxidative signal. This signal then engages kinase signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway and increases the activity of REDOX-sensitive transcription factors such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). To limit ROS overproduction and prevent oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant proteins such as superoxide dismutases (SODs) finely regulate signal intensity and are capable of terminating the oxidative signal when needed. Thus, oxidative signals, such as T cell activation, are well-controlled and critical for cellular communication.

Endoscopic Characterization and Outcome of COVID-19 Patients with Secondary Sclerosing Cholangitis: A Case Series of a Tertiary Center.

BACKGROUND AND AIMS: During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication. METHODS: 17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes. RESULTS: 258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation. CONCLUSIONS: COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.

Serum Adiponectin Predicts COVID-19 Severity.

Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. This study aimed to assess serum adiponectin levels in 26 healthy controls, as well as in 64 patients with moderate and 60 patients with severe COVID-19, to determine a potential association between serum adiponectin and the severity of COVID-19. Serum adiponectin levels in severe COVID-19 patients were significantly lower than in those with moderate disease and healthy controls, who exhibited similar serum adiponectin levels. Among patients with moderate disease, positive correlations were observed between serum adiponectin and C-reactive protein levels. Of note, serum adiponectin levels of severe COVID-19 cases were comparable between patients with and without dialysis or vasopressor therapy. Superinfection with bacteria did not exert a notable influence on serum adiponectin levels in patients with severe disease. Patients who were diagnosed with severe COVID-19 and vancomycin-resistant enterococci bacteremia showed a significant reduction in their serum adiponectin levels. An analysis conducted on the entire cohort, including both moderate and severe COVID-19 patients, showed that individuals who did not survive had lower serum adiponectin levels when compared to those who survived. In summary, this study highlights a decrease in serum adiponectin levels in severe COVID-19 cases, indicating the potential utility of adiponectin as an additional biomarker for monitoring disease severity in COVID-19 or critical illnesses in general.

Relationship between interprofessional collaboration and psychological distress experienced by healthcare professionals during COVID-19: a monocentric cross-sectional study.

Background: Since the onset of the COVID-19 pandemic, global healthcare systems have faced unprecedented challenges, leading to significant psychological distress among healthcare professionals. Recognizing the importance of enhanced interprofessional collaboration in alleviating this burden, as emphasized by the World Health Organization in 2020, we investigated whether such collaboration could mitigate staff psychological distress during crises. To our knowledge, no study has yet explored the role of interprofessional collaboration as a resilience factor in crises. Methods: For this monocentric cross-sectional study at a German university hospital, we examined the relationship between the quality of interprofessional collaboration and the psychological distress of healthcare professionals during the initial pandemic wave. We employed validated mental health instruments, such as the GAD-7 and PHQ-2, to assess anxiety and depressive symptoms. Additionally, custom-designed questionnaires evaluated "Pandemic-Associated Burden and Anxiety (PAB; PAA)" and interprofessional crisis management experiences. A novel "Interprofessional collaboration and communication (IPC)" assessment tool was developed based on international competency frameworks, demonstrating strong reliability. Results: The study involved 299 healthcare professionals (78.6% in direct contact with COVID-19 patients). Moderate levels of PAB/PAA were reported. However, a significant proportion experienced clinically relevant anxiety, as indicated by GAD-7. Negative IPC perceptions correlated with higher levels of psychological distress. Linear regression analysis showed associations between interprofessional collaboration and anxious and depressive symptoms, and pandemic-related burden. Conclusion: Our findings highlight the vital role of enhanced interprofessional collaboration in strengthening the psychological well-being of healthcare professionals during crises. The study underscores the need to foster a collaborative environment and integrate interprofessional education for resilience.

Evaluating the impact of interprofessional training wards on patient satisfaction and clinical outcomes: a mixed-methods analysis.

Introduction: Interprofessional teamwork is pivotal in modern healthcare, prompting the establishment of interprofessional training wards since 1996. While these wards serve as hubs for optimizing healthcare professional collaboration and communication, research into patient outcomes remains notably sparse and geographically limited, predominantly examining patient satisfaction and sparingly exploring other metrics like mortality or self-discharge rates. This study seeks to bridge this gap, comparing patient outcomes in interprofessional training wards and conventional wards under the hypothesis that the former offers no disadvantage to patient outcomes. Materials and methods: We explored patient outcomes within an interprofessional student ward called A-STAR at a University Hospital from October 2019 to December 2022. Engaging with patients discharged between May 2021 and April 2022, we utilized digital and paper-based anonymous questionnaires, catering to patient preference, to gather pertinent data. Results: Analysis of outcomes for 1,482 A-STAR (interprofessional student ward) and 5,752 conventional ward patients revealed noteworthy findings. A-STAR patients tended to be younger (59 vs. 61 years, p < 0.01) and more frequently male (73.5% vs. 70.4%, p = 0.025). Vital clinical outcomes, such as discharges against medical advice, complication-driven readmissions, and ICU transfers, were statistically similar between groups, as were mortality rates (1.2% vs. 1.3%, p = 0.468). A-STAR demonstrated high patient satisfaction, underscored by positive reflections on team competence, ward atmosphere, and responsiveness to concerns, emphasizing the value placed on interprofessional collaboration. Patient narratives commended team kindness, lucid explanations, and proactive involvement. Discussion: This data collectively underscores the safety and reliability of patient care within training wards, affirming that patients can trust the care provided in these settings. Patients on the interprofessional ward demonstrated high satisfaction levels: 96.7% appreciated the atmosphere and conduct of ward rounds. In comparison, 98.3% were satisfied with the discussion and information about their treatment during their hospital stay.

Serum Insulin-like Growth Factor-Binding Protein-2 as a Prognostic Factor for COVID-19 Severity.

Insulin-like growth factor-binding protein (IGFBP)-2 is a regulator of anabolic pathways, which become inactivated in severe illness. Here, we measured the serum IGFBP-2 levels of COVID-19 patients with moderate and severe disease as well as healthy controls to identify the associations of serum IGFBP-2 levels with disease severity. Patients with severe COVID-19 had higher serum IGFBP-2 levels than those with moderate disease and healthy controls, who had similar levels. Non-survivors of COVID-19 tended to have elevated serum IGFBP-2 levels compared to survivors. Increased serum IGFBP-2 levels were observed in patients requiring dialysis and vasopressor therapy. Serum IGFBP-2 was positively correlated with procalcitonin in both patient groups. Bacterial co-infection in severe COVID-19 patients did not influence serum IGFBP-2 levels. Patients with liver cirrhosis and obesity, showing increased and decreased serum IGFBP-2 levels, respectively, were excluded from the study. The present analysis showed that higher serum IGFBP-2 levels are associated with increased disease severity in COVID-19 patients. The similarity in serum IGFBP-2 levels between patients with moderate COVID-19 and healthy controls suggests that elevated IGFBP-2 is associated with critical illness rather than SARS-CoV-2 infection itself.