The role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been implicated in the pathogenesis of acquired hemophilia A (AHA). The aim of this study is to report our case and to summarize clinical studies on de novo AHA after SARS-CoV-2 infection. We performed a systematic search on the association of SARS-CoV-2 with AHA in four medical databases up to 28 May 2023. Eligible studies should include de novo AHA patients who had SARS-CoV-2 infection before or concomitant with the diagnosis of AHA. Findings were synthesized narratively. In addition, we report the case of a 62-year-old female patient, who presented to our clinic with left flank pain 2 weeks after SARS-CoV-2 infection. Clinical investigations confirmed AHA and imaging studies revealed retroperitoneal bleeding. Her hemostasis was successfully secured with bypassing agents; however, despite immunosuppressive therapy, high inhibitor titer persisted. In the systematic review, we identified only 12 relevant cases with a questionable cause–effect relationship between SARS-CoV-2 infection and AHA. Based on the qualitative analysis of the relevant publications, current clinical evidence is insufficient to support a cause–effect relationship. The analysis of data from ongoing AHA registries can serve further evidence.

A major complication of sepsis is the development of acute kidney injury (AKI). In case of acute tubular damage, Gc-globulin, a known serum sepsis marker is increasingly filtrated into the urine therefore, urinary Gc-globulin (u-Gc) levels may predict septic AKI. We developed and validated a competitive fluorescence ELISA method for u-Gc measurement. Serum and urine samples from septic patients were collected in three consecutive days (T1, T2, T3) and data were compared to controls. Intra- and interassay imprecisions were CV < 14% and CV < 20%, respectively, with a recovery close to 100%. Controls and septic patients differed (p < 0.001) in their u-Gc/u-creatinine levels at admission (T1, median: 0.51 vs. 79.1 µg/mmol), T2 (median: 0.51 vs. 57.8 µg/mmol) and T3 (median: 0.51 vs. 55.6 µg/mmol). Septic patients with AKI expressed higher u-Gc/u-creatinine values than those without AKI at T1 (median: 23.6 vs. 136.5 µg/mmol, p < 0.01) and T3 (median: 34.4 vs. 75.8 µg/mmol, p < 0.05). AKI-2 stage patients exhibited more increased u-Gc/u-creatinine levels at T1 (median: 207.1 vs. 53.3 µg/mmol, p < 0.05) than AKI-1 stage individuals. Moderate correlations (p < 0.001) were observed between u-Gc/u-creatinine and se-urea, se-creatinine, se-hsCRP, WBC, u-total protein, u-albumin, u-orosomucoid/u-creatinine, and u-Cystatin C/u-creatinine levels. U-Gc testing may have a predictive value for AKI in septic patients.

Background: The actin-binding protein Flightless-I (Flii) has not been quantified in the human serum yet. We aimed to determine serum Flii levels in healthy individuals and to investigate Flii as a potential marker in patients with sepsis focusing on diagnosis, organ failures, and short-term mortality. Methods: A total of 30 controls and 64 septic and 22 non-septic patients were enrolled in this follow-up study. Serum Flii levels were quantified by using the capillary electrophoresis-based Simple Western™ system with chemiluminescent detection. The assay was calibrated by applying dilution series of a purified recombinant human Flii standard and a parallel internal standard. Results: Flii levels of healthy controls were found between 3.5 and 8.8 mg/L, while septic and non-septic patients showed significantly lower values (p < 0.001). First-day Flii could differentiate sepsis from the non-septic inflammatory state (AUC: 0.667; p < 0.05) and indicated acute respiratory distress syndrome (ARDS) among septic patients (AUC: 0.686; p < 0.05). Furthermore, a combination of Flii and other sepsis markers seemed to offer an improved diagnostic performance (sepsis vs. non-sepsis, AUC of Flii + gelsolin (GSN) + Gc-globulin + procalcitonin: 0.974; p < 0.001 and ARDS vs. non-ARDS, AUC of Flii + GSN + presepsin: 0.776; p < 0.001) compared with single markers even in the prediction of 14-day mortality (AUC of Flii + GSN + Gc-globulin: 0.76; p < 0.001). Conclusions: We adapted a properly precise and reproducible automated Western blot method to determine concentrations of Flii in human serum. Our results revealed the relationship between Flii and sepsis; however, Flii alone did not appear to be a prominent sepsis marker. When combined with other biomarkers, measurement of serum Flightless-I may provide additional value supporting patient care.

Background/Objectives: Intensive care unit-acquired weakness (ICUAW) is a frequent complication characterized by symmetrical and proximal limb muscle weakness. Its diagnosis is primarily based on clinical symptoms; however, ICUAW assessment can often be uncertain. Blood biomarkers have not yet been widely investigated for this purpose. Serum gelsolin (GSN) is synthesized by skeletal muscle cells. It plays a crucial role in binding extracellular actin filaments and pro-inflammatory cytokines. In sepsis-associated ICUAW, GSN levels might massively decrease due to their buffering activity and muscle wasting. We elucidated the predictive capacity of GSN regarding ICUAW and its additional diagnostic/prognostic potential in sepsis compared to classical parameters. Methods: We recruited septic and non-septic ICU patients for our follow-up study. Patients were retrospectively categorized into ICUAW positive (n = 26) and negative (n = 47) groups based on their clinical characteristics. Sera were collected on the 1st, 2nd and 3rd days of ICU stay. Ambulatory patients (n = 34) served as controls. GSN levels were measured by our previously developed automated immunoturbidimetric assay. Clinical and laboratory parameters were collected from our hospital information system. Results: Admission GSN levels were significantly reduced in ICU patients compared to controls (median: 11.60 vs. 75.99 mg/L). ICUAW positive patients had significantly lower admission GSN levels than ICUAW negative patients (median: 8.10 vs. 14.30 mg/L), and a similar tendency was observed during follow-up. GSN showed predictive capacity regarding ICUAW (ROC AUC: 0.711, p < 0.01), especially when combined with albumin (ROC AUC: 0.750, p < 0.01). The combination of admission GSN, albumin, and procalcitonin demonstrated significant diagnostic performance (ROC AUC: 0.803) regarding the requirement for invasive ventilation, and GSN had prognostic value for 28-day mortality as well. Conclusions: GSN might serve as an intriguing marker in the prediction of ICUAW, especially when combined with albumin. The parallel decline of GSN and albumin could reflect the combined effects of systemic inflammation and muscle wasting seen in ICUAW.