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1.
The risk of hepatitis B virus reactivation in COVID-19 patients treated with corticosteroids : a retrospective observational cohort study
Daša Stupica, Stefan Collinet-Adler, Janina Jerman Grašič, Deja Juriševič, Nataša Kejžar, Mario Poljak, Tina Štamol, 2026, original scientific article

Abstract: Background: Systemic corticosteroids, recommended for adult patients with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, may carry an increased risk of reactivating latent infections such as hepatitis B virus (HBV) infection. Methods: This retrospective observational cohort study of prospectively collected clinical data evaluated HBV screening frequency and examined the prevalence and reactivation of HBV among hospitalised adults treated with systemic corticosteroids for COVID-19 at a tertiary care hospital in Slovenia. Results: Anti-HBc screening was conducted in 1,793/2,134 (84%) hospitalised patients receiving corticosteroids for COVID-19 (median age 70 years [IQR 59‒79 years]; 1,082 [60.3%] were male). Among the 1,793 screened patients, 157 (8.8%) were anti-HBc positive, and 5 (0.3%) of them also HBsAg positive. All five HBsAg-positive patients were aviremic. HBV infection was previously known in three of these patients (two on long-term tenofovir treatment) and identified de novo in two. Entecavir was initiated for one patient. Throughout the hospitalisations and 12-month follow-up periods, no cases of HBV viral rebound were observed in any of the HBsAg positive patients; one of the treated patients succumbed to COVID-19 pneumonia. No HBV reactivation or unexplained hepatopathy occurred in the 152 anti-HBc positive/HBsAg negative patients, none of whom were given antiviral prophylaxis. Conclusions: Corticosteroids for COVID-19 did not appear to be a significant risk factor for HBV reactivation in cases of occult hepatitis B. Universal antiviral prophylaxis in HBsAg negative/anti HBc positive individuals may not be warranted with short courses of corticosteroids for COVID-19 in the absence of other risk factors for HBV reactivation.
Keywords: COVID-19, corticosteroids, hepatitis B virus, reactivation
Published in DiRROS: 15.05.2026; Views: 20; Downloads: 15
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2.
Ten-year trends in serum 25-hydroxyvitamin D in Slovenia (2014–2023) : laboratory-based data from tested individuals and COVID-19-period changes
Joško Osredkar, Darko Siuka, Aleš Jerin, Borut Štabuc, Uroš Godnov, 2026, original scientific article

Abstract: Background: Vitamin D status is influenced by season, age, and public health messaging. The COVID-19 pandemic was accompanied by heightened interest in vitamin D, but long-term national data from Central/Eastern Europe remain limited. We aimed to characterize 10-year trends, seasonal variation, and demographic determinants of serum 25-hydroxyvitamin D [25(OH)D] in Slovenia, with particular focus on changes during the COVID-19 period. Methods: We performed a retrospective cross-sectional analysis of all serum 25(OH)D measurements performed at the Slovenian national reference laboratory between January 2014 and December 2023. The core analytic cohort included 106,875 patients with valid 25(OH)D results, aged 0–100 years. Vitamin D status was classified as deficient (<30 nmol/L), insufficient (30–50 nmol/L), adequate (50–75 nmol/L), and optimal (>75 nmol/L). Temporal trends, seasonal patterns, and age- and sex-specific differences were assessed using non-parametric tests and Kendall’s τ. Results: Mean 25(OH)D concentration over the study period was 61.9 ± 34.2 nmol/L; 16.0% of patients were deficient and 22.8% insufficient. Annual mean 25(OH)D increased from 57.0 nmol/L in 2014 to 67.2 nmol/L in 2023, with a significant upward temporal trend and a 14.6% higher mean level during 2020–2023 compared with 2014–2019. Seasonal variation was pronounced (≈20% higher summer–autumn vs. winter–spring), and vitamin D status declined progressively with age, with the highest deficiency prevalence in patients ≥ 70 years. Females had slightly higher 25(OH)D than males, although absolute differences were small. Conclusions: This laboratory-based analysis of tested patients showed higher 25(OH)D concentrations during and after the COVID-19 period, superimposed on persistent seasonal and age-related gradients. These observations identify older adults and winter testing periods as important contexts for vitamin D optimization, but they should be interpreted as descriptive trends among tested individuals rather than as evidence of causal pandemic effects or population-wide prevalence changes.
Keywords: 25-hydroxyvitamin D, seasonal variation, deficiency, age factors, COVID-19 pandemic
Published in DiRROS: 24.04.2026; Views: 174; Downloads: 106
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3.
Functional neurological disorder following COVID-19 : results from a Large International Electronic Health Record Database
Rok Berlot, Livia Asan, Timothy R. Nicholson, Biba Stanton, Thomas A. Pollak, Mark J. Edwards, 2025, original scientific article

Abstract: Background: Following COVID-19, an increased risk of neurological and psychiatric sequelae has been reported. Viral illnesses commonly trigger functional neurological disorder (FND). However, mechanisms beyond immediate biological effects may contribute to FND after COVID-19. While FND cases have been observed after COVID-19, the overall risk and contributing factors remain unclear. In this retrospective cohort study, we compared the rates of FND post-COVID-19 to other respiratory tract infections (RTIs), assessed the influence of disease severity, and the characteristics of newly diagnosed patients. Methods: We used TriNetX, a global electronic health record network. In total, 2,740,094 COVID-19 cases and 1846 post-COVID-19 FND cases were analysed. We compared FND incidence between 2 weeks and 6 months after COVID-19 to other RTIs and across cohorts of varying COVID-19 severity. Characteristics of individuals with new diagnoses of FND and migraine following COVID-19 were compared. Results: The incidence of FND was higher in COVID-19 patients with records of hospitalisation (OR 2.165; 95% CI 1.691-2.773) and emergency department visits (OR 1.412; 95% CI 1.069-1.864). Incidence was higher following COVID-19 compared to other RTIs, both in the first 2 years of the pandemic (0.033 vs. 0.021%, OR 1.555, 95% CI 1.271-1.902) and subsequently (0.038 vs. 0.027%, OR 1.394, 95% CI 1.173-1.657). Medical, neurological, and psychiatric comorbidities were more common in newly diagnosed post-COVID-19 FND compared to migraine. Conclusions: New-onset FND appears more likely after COVID-19 than other RTIs. Both the severity of the triggering illness and pre-existing individual vulnerability may contribute to the development of FND.
Keywords: COVID-19, conversion disorder, functional neurological disorder, neuropsychiatric manifestations, risk factors
Published in DiRROS: 10.04.2026; Views: 207; Downloads: 130
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4.
Integrative vitamin D-inflammatory-coagulation biomarker index predicts COVID-19 severity : development and validation of the vitamin D inflammatory burden score (VDIBS)
Joško Osredkar, Uroš Godnov, Darko Siuka, 2026, original scientific article

Abstract: Vitamin D deficiency is common in hospitalized COVID-19 patients and is associated with increased severity. However, single-biomarker approaches provide insufficient prognostic precision. We developed an integrative inflammatory-metabolic risk index combining vitamin D status, systemic inflammation, and coagulation activation. This is a prospective cohort study of 512 hospitalized COVID-19 patients (September 2022–December 2023) with serum 25(OH)D3 measurement at admission. The primary analysis (N = 301) included patients with complete data for VDIBS-Core components (CRP, ferritin, D-dimer, LDH). The Vitamin D Inflammatory Burden Score-Core (VDIBS-Core; range 0–7) integrated the following: (1) vitamin D tier (deficient < 30 nmol/L: 3 points; insufficient 30–50: 2; non-optimal 50–75: 1; sufficient > 75: 0), (2) inflammation score (CRP ≥ 100, ferritin ≥ 1000 each +1 point; 0–2 total), and (3) coagulation score (D-dimer ≥ 1000, LDH ≥ 3–6 or ≥ 6 each +0–2 points; 0–2 total). The IL-6 measurement (N = 48, 9.4%) was explored separately as VDIBS-Plus in the secondary analysis. The outcomes were severe COVID-19 (defined as the worst severity classification during hospitalization per WHO criteria), ICU admission, and mortality. The mean vitamin D was 63.4 ± 33.2 nmol/L (68.1% deficient). Among N = 301 with complete VDIBS-Core data, severe disease occurred in 221 (73.4%), ICU admission in 15 (5.0%), and mortality in 8 (2.7%). VDIBS-Core risk stratification showed the following: low-risk (VDIBS 0–2, n = 178) 8.4% severe; moderate-risk (VDIBS 3–5, n = 245) 45.7% severe; and high-risk (VDIBS 6–7, n = 89) 78.6% severe; χ2 = 142.3, p < 0.001. VDIBS-Core predicted severe disease with AUC 0.78 (95% CI 0.74–0.82), with excellent calibration (Hosmer–Lemeshow p = 0.40). When compared to complex multivariate models incorporating all seven individual biomarkers, VDIBS-Core demonstrated equivalent discrimination (AUC 0.82, Δ = 0.04, p = 0.08, not statistically significant) with superior clinical simplicity. Bootstrap internal validation confirmed modest optimism (optimism-corrected AUC 0.76). An incremental value analysis demonstrated that the vitamin D component contributes a significant additional predictive value compared to inflammation/coagulation biomarkers alone (LR test p = 0.004). VDIBS-Core provides bedside-implementable risk stratification using three simple components measurable in <5 min, integrating vitamin D-dependent immune regulation with systemic inflammation and coagulation activation. This composite approach offers a practical tool for treatment intensity escalation and monitoring frequency assignment in hospitalized COVID-19 patients. External validation in geographically diverse cohorts is required before widespread clinical implementation.
Keywords: vitamin D deficiency, COVID-19 severity, biomarker integration, risk stratification, immunometabolism
Published in DiRROS: 08.04.2026; Views: 167; Downloads: 100
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5.
Age-related effects of COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI : results of the ISACS-STEMI COVID-19 registry
Giuseppe De Luca, Magdy Algowhary, Berat Uguz, Dinaldo C. Oliveira, Vladimir Ganyukov, Oliver Busljetik, Miha Čerček, 2023, original scientific article

Abstract: Background: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. Methods: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March–June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. Results: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825–0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24–1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05–1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.
Keywords: ageing, ST-segment elevation myocardial infarction, COVID-19
Published in DiRROS: 31.03.2026; Views: 195; Downloads: 86
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6.
Impact of smoking status on mortality in STEMI patients undergoing mechanical reperfusion for STEMI : insights from the ISACS–STEMI COVID-19 registry
Giuseppe De Luca, Magdy Algowhary, Berat Uguz, Dinaldo C. Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Čerček, 2022, original scientific article

Abstract: The so-called “smoking paradox”, conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS–STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.
Keywords: myocardial infarction, smoking paradox, percutaneous coronary intervention, COVID-19, mortality
Published in DiRROS: 31.03.2026; Views: 200; Downloads: 82
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7.
Renin-angiotensin system inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID-19 pandemic
Giuseppe De Luca, Matteo Nardin, Magdy Algowhary, Berat Uguz, Dinaldo C. Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Čerček, Lisette Okkels Jensen, Poay Huan Loh, 2021, original scientific article

Abstract: Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensinconverting-enzyme (ACE)2 and patient’s susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment. Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients. Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010. Conclusions: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both preadmission chronic RASI therapy and in-hospital RASI did not negatively affected patients’ survival during the hospitalization, neither increased the risk of SARS-CoV2 infection.
Keywords: RAAS inhiibitors, mortality, diabetes, STEMI, COVID-19
Published in DiRROS: 24.03.2026; Views: 257; Downloads: 168
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8.
Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic : insights from the international multicenter ISACS-STEMI registry
Giuseppe De Luca, Matteo Nardin, Magdy Algowhary, Berat Uguz, Dinaldo C. Oliveira, Vladimir Ganyukov, Zan Zimbakov, Miha Čerček, Lisette Okkels Jensen, Poay Huan Loh, 2022, original scientific article

Abstract: Background: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclero‑ sis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocar‑ dial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. Methods: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with pri‑ mary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. Results: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dis‑ similarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P=0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjust‑ ment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI]=0.913[0.658–1.266], P=0.585) nor for 30-days mortality (adjusted OR [95% CI]=0.850 [0.620–1.164], P=0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. Conclusion: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline charac‑ teristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity.
Keywords: COPD, STEMI, COVID-19
Published in DiRROS: 24.03.2026; Views: 247; Downloads: 147
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9.
Gender difference in the effects of COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI : results of the ISACS-STEMI COVID-19 registry
Giuseppe De Luca, Stephane Manzo-Silberman, Magdy Algowhary, Berat Uguz, Dinaldo C. Oliveira, Vladimir Ganyukov, Oliver Busljetik, Miha Čerček, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, 2023, original scientific article

Abstract: Background. Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. Methods. This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March–June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. Results. We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825–0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31–2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96–1.34], p = 0.12). Conclusions. The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females.
Keywords: gender, COVID-19, mortality, STEMI
Published in DiRROS: 24.03.2026; Views: 232; Downloads: 128
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10.
Serum vitamin D and inflammatory markers in SARS-CoV-2 positive pregnant women
Vita Andreja Mesarič, Tanja Premru-Sršen, Gorazd Kavšek, Ivan Verdenik, Aleksandra Štrukelj, Mirjam Druškovič, 2026, original scientific article

Abstract: Objectives: The SARS-CoV-2 pandemic was declared by World Health Organisation (WHO) in March 2020, causing health and economic disruptions and millions of deaths. Pregnant women represent a vulnerable group, as COVID-19 during pregnancy increases the risk of preterm birth, preeclampsia, and severe maternal illness. Nutritional status, such as vitamin D deficiency, may influence these outcomes, yet data on its status in the cohort of SARS-CoV-2 positive pregnant women as well as its association with inflammatory and angiogenic markers is scarce. The aim of this study was to evaluate the levels of vitamin D in the cohort of SARSCoV- 2 positive pregnant women and its association with inflammatory and angiogenic markers. Methods: Prospective cohort study at Ljubljana Maternity Hospital (Oct 1, 2020–Mar 30, 2021) enrolled singleton pregnancies with PCR-confirmed SARS-CoV-2 within the last 14 days, delivering at our institution. Results: Among 235 SARS-CoV-2-positive pregnant women 62.1% had adequate and 21.3% insufficient level of vitamin D and 13.6%were vitaminDdeficient. Statistical analysis revealed no significant correlations between 25-OH-vitamin D and Creactive protein (CRP), procalcitonin (PCT), leukocyte count, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), the sFlt-1/PlGF ratio, or body mass index (BMI). Conclusions: Our prospective cohort study revealed that high proportion of pregnant women has inadequate levels of vitamin D. Although maternal insufficiency is linked to adverse outcomes, its association with inflammatory and angiogenic markers remains unclear. Rigorous studies in pregnancy are essential to clarify vitamin D’s role in COVID-19 complications in pregnancy.
Keywords: COVID-19, pandemic, pregnancy, SARS-CoV-2, vitamin D deficiency, inflammation
Published in DiRROS: 19.03.2026; Views: 248; Downloads: 176
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