Longitudinal Analysis of Antiphospholipid Antibody Dynamics after Infection with SARS-CoV-2 or Vaccination with BNT162b2.

Antiphospholipid antibodies (aPL) comprise a group of autoantibodies that reflect prothrombotic risk in antiphospholipid syndrome (APS) but may also be present in a small proportion of healthy individuals. They are often transiently elevated in infections, including SARS-CoV-2, and may also be associated with vaccine-induced autoimmunity. Therefore, we aimed to investigate the dynamics of aPL in COVID-19 patients and in individuals (healthcare professionals-HCPs) after receiving BNT162b2 vaccine and to compare aPL levels and positivity with those found in APS patients. We measured solid-phase identifiable aPL, including anticardiolipin (aCL), anti-ß2 glycoprotein I (anti-ß2GPI), and anti-prothrombin/phosphatidylserine (aPS/PT) antibodies in 58 HCPs before and after vaccination (at 3 weeks, 3, 6, and 9 months after the second dose, and 3 weeks after the third booster dose), in 45 COVID-19 patients hospitalized in the ICU, in 89 COVID-19 patients hospitalized in the non-ICU (at admission, at hospital discharge, and at follow-up), and in 52 patients with APS. The most frequently induced aPL in COVID-19 patients (hospitalized in non-ICU) were aCL (50.6% of patients had positive levels at at least one time point), followed by anti-ß2GPI (21.3% of patients had positive levels at at least one time point). In 9/89 COVID-19 patients, positive aPL levels persisted for three months. One HCP developed aCL IgG after vaccination but the persistence could not be confirmed, and two HCPs developed persistent anti-ß2GPI IgG after vaccination with no increase during a 1-year follow-up period. Solid-phase aPL were detected in 84.6% of APS patients, in 49.4% of COVID-19 patients hospitalized in the non-ICU, in 33.3% of COVID-19 patients hospitalized in the ICU, and in only 17.2% of vaccinated HCPs. aPL levels and multiple positivity were significantly lower in both infected groups and in vaccinated individuals compared with APS patients. In conclusion, BNT162b2 mRNA vaccine may have induced aPL in a few individuals, whereas SARS-CoV-2 infection itself results in a higher percentage of aPL induction, but the levels, persistence, and multiple positivity of aPL do not follow the pattern observed in APS.

Incidence and Risk Factors for Clostridioides difficile Infections in Non-COVID and COVID-19 Patients: Experience from a Tertiary Care Hospital.

(1) Background: The aim of this study was to assess the incidence and the risk factors for healthcare-associated Clostridioides difficile infection (HA-CDI) in patients with COVID-19 and without this infection. (2) Methods: A single-center, prospective observational study was conducted at the University Clinical Hospital Center in Belgrade, Serbia, from January 2019 to December 2021. The entire hospital was a COVID-dedicated hospital for 12 months during the study period. The incidence density rates and risk factors for HA-CDI in patients with and without COVID-19 are presented. (3) Results: The incidence rates of HA-CDIs were three times higher in patients with COVID-19. The HA-CDI-COVID-patients were younger (69.9 ± 12.6 vs. 72.5 ± 11.6; p = 0.017), admitted from another hospital (20.5% vs. 2.9; p < 0.001), had antimicrobial therapy before CDI (99.1% vs. 91.3%, p < 0.001), received two or more antibiotics (p = 0.030) during a longer period (p = 0.035), received proton pump inhibitors (95.9% vs. 50.0%, p < 0.001) during a longer period (p = 0.012) and steroids (32.8% vs. 20.4%, p < 0.001). During the last month before their current hospitalization, a higher percentage of patients without COVID-19 disease were hospitalized in our hospital (p < 0.001). Independent predictors for HA-CDIs in patients with COVID-19 were admission from another hospital (p = 0.003), the length of antibiotic administration (0.020), and the use of steroids in therapy (p < 0.001). The HA-CDI predictors in the non-COVID patients were older age (p = 0.017), advanced-stage renal failure (p = 0.005), chemotherapy (p = 0.003), and a low albumin level (0.005). (4) Conclusion: Higher incidence rates of HAI-CDIs in COVID-19 patients did not occur due to reduced infection control precautions and hygiene measures but due to antibiotic therapy and therapy with other drugs used during the pandemic.

Characteristics and Outcomes of Patients with Acute Coronary Syndrome and COVID-19.

Acute coronary syndrome (ACS) in patients with COVID-19 is triggered by various mechanisms and can significantly affect the patient's further treatment and prognosis. The study aimed to investigate the characteristics, major complications, and predictors of mortality in COVID-19 patients with ACS. All consecutive patients hospitalized from 5 July 2020 to 5 May 2021 for ACS with confirmed SARS-Co-2 were prospectively enrolled and tracked for mortality until 5 June 2021. Data from the electronic records for age and diagnosis, matched non-COVID-19 and COVID-19 ACS group, were extracted and compared. Overall, 83 COVID-19 ACS patients, when compared to 166 non-COVID ACS patients, had significantly more prevalent comorbidities, unfavorable clinical characteristics on admission (acute heart failure 21.7% vs. 6.6%, p < 0.01) and higher rates of major complications, 33.7% vs. 16.8%, p < 0.01, and intrahospital 30-day mortality, 6.7% vs. 26.5%, p < 0.01. The strongest predictors of mortality were aortic regurgitation, HR 9.98, 95% CI 1.88; 52.98, p < 0.01, serum creatinine levels, HR 1.03, 95% CI 1.01; 1.04, p < 0.01, and respiratory failure therapy, HR 13.05, 95% CI 3.62; 47.01, p < 0.01. Concomitant ACS and COVID-19 is linked to underlying comorbidities, adverse presenting features, and poor outcomes. Urgent strategies are needed to improve the outcomes of these patients.

Sex differences and disparities in cardiovascular outcomes of COVID-19.

AIMS: Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. METHODS AND RESULTS: This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04). CONCLUSIONS: Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Bradykinin and Galectin-3 in Survived and Deceased Patients with COVID-19 Pneumonia: An Increasingly Promising Biochemical Target

Introduction There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. Aim The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients' admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. Results The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). Conclusion The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.

Point-of-Care Echocardiographic Characteristics of COVID-19 Patients with Pulmonary Embolism.

INTRODUCTION: Thrombotic complications, such as pulmonary embolism, are common in COVID-19 patients. Point-of-care ultrasound is a highly recommended tool for orientation in critically ill patients with suspected or confirmed complications. METHODS: An observational study was conducted on 32 consecutive patients with confirmed pulmonary embolism and COVID-19 infection treated in the Intensive Care Unit of the University Hospital Medical Center "Bezanijska kosa", Belgrade, Serbia, between April 2021 and March 2022. Predictors of the need for oxygen support were determined, while point-of-care echocardiographic parameters and various anamnestic, laboratory, and clinically significant parameters were correlated with the Pulmonary Embolism Severity Index (PESI) score. RESULTS: More than two-thirds of patients in our study had PE symptoms present at hospital admission (68.8%). The majority of patients had segmental pulmonary embolism (48.4%), with high to very high PESI score values in 31.3% of patients. Pneumonia was present in 68.8% of the study population. The PESI score was negatively correlated with diastolic blood pressure and SaO2 at the time of PE diagnosis, LV ejection fraction, and PVAT. A positive correlation was found between the PESI score, maximum CRP, and D-dimer at the time of PTE diagnosis. A larger right ventricular diameter was associated with a greater need for oxygen support. CONCLUSION: Point-of-care echocardiography is a valuable tool for the risk assessment of COVID-19 patients with pulmonary embolism. Right ventricular size stood out as a significant marker of disease severity.

Thrombosis risk assessment in patients with congenital thrombophilia during COVID - 19 infection.

BACKGROUND: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infection, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. METHODS: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 patients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. RESULTS: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with thrombophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. CONCLUSION: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.

Elevated Transaminases as Predictors of COVID-19 Pneumonia Severity.

BACKGROUND: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. METHODS: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. RESULTS: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). CONCLUSION: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.

Acute Coronary Syndrome in the COVID-19 Era-Differences and Dilemmas Compared to the Pre-COVID-19 Era.

The COVID-19 pandemic has led to numerous negative implications for all aspects of society. Although COVID-19 is a predominant lung disease, in 10-30% of cases, it is associated with cardiovascular disease (CVD). The presence of myocardial injury in COVID-19 patients occurs with a frequency between 7-36%. There is growing evidence of the incidence of acute coronary syndrome (ACS) in COVID-19, both due to coronary artery thrombosis and insufficient oxygen supply to the myocardium in conditions of an increased need. The diagnosis and treatment of patients with COVID-19 and acute myocardial infarction (AMI) is a major challenge for physicians. Often the presence of mixed symptoms, due to the combined presence of COVID-19 and ACS, as well as possible other diseases, nonspecific changes in the electrocardiogram (ECG), and often elevated serum troponin (cTn), create dilemmas in diagnosing ACS in COVID-19. Given the often-high ischemic risk, as well as the risk of bleeding, in these patients and analyzing the benefit/risk ratio, the treatment of patients with AMI and COVID-19 is often associated with dilemmas and difficult decisions. Due to delays in the application of the therapeutic regimen, complications of AMI are more common, and the mortality rate is higher.

Seroprevalence in health care workers during the later phase of the second wave: Results of three hospitals in Serbia, prior to vaccine administration.

BACKGROUND: Since the COVID-19 pandemic has started, Serbia has faced problems in implementing proper public health measures in the population, including non-pharmaceutical interventions, as well as protecting health care workers (HCWs) from disease, like all other countries. This study aimed to estimate COVID-19 seroprevalence and evaluate the risk perception of COVID-19 among HCWs in three different hospitals in Belgrade, Serbia: non-COVID hospital, Emergency Center (EC), and dedicated COVID hospital. METHODS: A cross-sectional study was conducted in three hospitals during the second wave of the outbreak in Serbia, from June to early October. All staff in these hospitals were invited to voluntarily participate in blood sampling for IgG antibodies against SARS-CoV-2 and questionnaire testing. The questionnaire included socio-demographic characteristics, known exposure to COVID-19 positive persons, previous signs and symptoms related to COVID-19 infection since the outbreak had started in our country, and SARS-CoV-2 PCR testing. RESULTS: The overall prevalence of SARS-CoV-2 antibody among 1580 HCWs was 18.3 % [95 % CI 16.4-20.3 %]. Significantly higher prevalence of HCWs with positive results for the serum IgG antibody test was observed in COVID hospital (28.6 %, 95 %CI: 24.0-33.6 %) vs. prevalence in the EC (12.6 %, 95 %CI: 10.1-15.4 %), and in the non-COVID hospital (18.3 %, 95 %CI: 15.2-26.7 %). The prevalence adjusted for declared test sensitivity and specificity would be 16.8 %; that is 27.4 % in COVID-19 hospital, 10.9 % in EC, and 16.8 % in non-COVID hospital. In multivariate logistic regression analysis, the independent predictors for seropositivity were working in COVID-hospital, the profession of physician, and the presence of the following symptoms: fever, shortness of breath, and anosmia/ageusia. CONCLUSIONS: We found an overall seropositivity rate of 18.3 % and 16.0 % of the adjusted rate that is higher than seroprevalence obtained in similar studies conducted before vaccinations started. The possibility that patients in non-COVID dedicated hospitals might also be infectious, although PCR tested, imposes the need for the use of personal protective equipment also in non-COVID medical institutions.

COVID-19 Vaccination Willingness and Vaccine Uptake among Healthcare Workers: A Single-Center Experience.

Healthcare workers (HCWs) are at higher risk of developing COVID-19 due to their professional exposition to the SARS-CoV-2 virus. This study assesses the intention of vaccination against COVID-19 before the vaccines were approved, and the rate of vaccine uptake during the first nine months of immunization among HCWs. A cross-sectional seroprevalence study was carried out during July 2020 in University Clinical Hospital Center Bezanijska Kosa in Belgrade, Serbia that included 62.8% of all HCWs. Besides serological testing for IgG antibodies, data about HCWs' intention to accept COVID-19 vaccination if a vaccine became available were collected. This cohort of HCWs was followed up until the end of October 2021 to assess the number of vaccinated and PCR-positive staff. In the cross-sectional study, 18.3% HCWs had positive SARS-CoV-2 IgG antibodies without difference with IgG-negative HCWs regarding age, gender, profession type, and years of service. Before vaccines became available, a significantly higher percentage of IgG-positive HCWs compared to IgG-negative HCWs was unsure whether to be vaccinated (62.5% vs. 49.0%), and significantly fewer stated that they would not be vaccinated (16.7% vs. 25.1%). When the vaccines became available in Serbia, among IgG-negative HCWs, those who stated clear positive (yes) and clear negative (no) attitude toward vaccination before the immunization period had begun were vaccinated at 28% and 20%, respectively, while 51% of unsure HCWs received a vaccine (p = 0.006). Among IgG-positive HCWs, there was no statistical difference in vaccine uptake regarding those with previous negative, positive, and unsure opinions about vaccination (p = 0.498). In multivariate analysis, independent factors associated with uptake were being female (OR = 1.92; 95%CI: 1.04-3.55), age of 30-59 years, previously vaccine-unsure (OR = 1.84; 95%CI: 1.04-3.25), and those with previous positive vaccine attitudes (OR = 2.48; 95%CI:1.23-5.01), while nurses were less likely to become vaccinated (OR = 0.39 95% CI: 0.20-0.75) These findings indicate a positive change in attitudes of HCWs towards COVID-19 vaccination.

D-dimer, CRP, PCT, and IL-6 Levels at Admission to ICU Can Predict In-Hospital Mortality in Patients with COVID-19 Pneumonia.

INTRODUCTION: Health care workers have had a challenging task since the COVID-19 outbreak. Prompt and effective predictors of clinical outcomes are crucial to recognize potentially critically ill patients and improve the management of COVID-19 patients. The aim of this study was to identify potential predictors of clinical outcomes in critically ill COVID-19 patients. METHODS: The study was designed as a retrospective cohort study, which included 318 patients treated from June 2020 to January 2021 in the Intensive Care Unit (ICU) of the Clinical Hospital Center "Bezanijska Kosa" in Belgrade, Serbia. The verified diagnosis of COVID-19 disease, patients over 18 years of age, and the hospitalization in ICU were the criteria for inclusion in the study. The optimal cutoff value of D-dimer, CRP, IL-6, and PCT for predicting hospital mortality was determined using the ROC curve, while the Kaplan-Meier method and log-rank test were used to assess survival. RESULTS: The study included 318 patients: 219 (68.9%) were male and 99 (31.1%) female. The median age of patients was 69 (60-77) years. During the treatment, 195 (61.3%) patients died, thereof 130 male (66.7%) and 65 female (33.3%). 123 (38.7%) patients were discharged from hospital treatment. The cutoff value of IL-6 for in-hospital death prediction was 74.98 pg/mL (Sn 69.7%, Sp 62.7%); cutoff value of CRP was 81 mg/L (Sn 60.7%, Sp 60%); cutoff value of procalcitonin was 0.56 ng/mL (Sn 81.1%, Sp 76%); and cutoff value of D-dimer was 760 ng/mL FEU (Sn 63.4%, Sp 57.1%). IL-6 ≥ 74.98 pg/mL, CRP ≥ 81 mg/L, PCT ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL were statistically significant predictors of in-hospital mortality. CONCLUSION: IL-6 ≥ 74.98 pg/mL, CRP values ≥ 81 mg/L, procalcitonin ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL could effectively predict in-hospital mortality in COVID-19 patients.

COVID-19 Vaccination Willingness and Vaccine Uptake among Healthcare Workers: A Single-Center Experience

Healthcare workers (HCWs) are at higher risk of developing COVID-19 due to their professional exposition to the SARS-CoV-2 virus. This study assesses the intention of vaccination against COVID-19 before the vaccines were approved, and the rate of vaccine uptake during the first nine months of immunization among HCWs. A cross-sectional seroprevalence study was carried out during July 2020 in University Clinical Hospital Center Bezanijska Kosa in Belgrade, Serbia that included 62.8% of all HCWs. Besides serological testing for IgG antibodies, data about HCWs' intention to accept COVID-19 vaccination if a vaccine became available were collected. This cohort of HCWs was followed up until the end of October 2021 to assess the number of vaccinated and PCR-positive staff. In the cross-sectional study, 18.3% HCWs had positive SARS-CoV-2 IgG antibodies without difference with IgG-negative HCWs regarding age, gender, profession type, and years of service. Before vaccines became available, a significantly higher percentage of IgG-positive HCWs compared to IgG-negative HCWs was unsure whether to be vaccinated (62.5% vs. 49.0%), and significantly fewer stated that they would not be vaccinated (16.7% vs. 25.1%). When the vaccines became available in Serbia, among IgG-negative HCWs, those who stated clear positive (yes) and clear negative (no) attitude toward vaccination before the immunization period had begun were vaccinated at 28% and 20%, respectively, while 51% of unsure HCWs received a vaccine (p = 0.006). Among IgG-positive HCWs, there was no statistical difference in vaccine uptake regarding those with previous negative, positive, and unsure opinions about vaccination (p = 0.498). In multivariate analysis, independent factors associated with uptake were being female (OR = 1.92;95%CI: 1.04–3.55), age of 30–59 years, previously vaccine-unsure (OR = 1.84;95%CI: 1.04–3.25), and those with previous positive vaccine attitudes (OR = 2.48;95%CI:1.23–5.01), while nurses were less likely to become vaccinated (OR = 0.39 95% CI: 0.20–0.75) These findings indicate a positive change in attitudes of HCWs towards COVID-19 vaccination.

Characteristics and Outcomes of Patients with Acute Coronary Syndrome and COVID-19

Acute coronary syndrome (ACS) in patients with COVID-19 is triggered by various mechanisms and can significantly affect the patient's further treatment and prognosis. The study aimed to investigate the characteristics, major complications, and predictors of mortality in COVID-19 patients with ACS. All consecutive patients hospitalized from 5 July 2020 to 5 May 2021 for ACS with confirmed SARS-Co-2 were prospectively enrolled and tracked for mortality until 5 June 2021. Data from the electronic records for age and diagnosis, matched non-COVID-19 and COVID-19 ACS group, were extracted and compared. Overall, 83 COVID-19 ACS patients, when compared to 166 non-COVID ACS patients, had significantly more prevalent comorbidities, unfavorable clinical characteristics on admission (acute heart failure 21.7% vs. 6.6%, p < 0.01) and higher rates of major complications, 33.7% vs. 16.8%, p < 0.01, and intrahospital 30-day mortality, 6.7% vs. 26.5%, p < 0.01. The strongest predictors of mortality were aortic regurgitation, HR 9.98, 95% CI 1.88;52.98, p < 0.01, serum creatinine levels, HR 1.03, 95% CI 1.01;1.04, p < 0.01, and respiratory failure therapy, HR 13.05, 95% CI 3.62;47.01, p < 0.01. Concomitant ACS and COVID-19 is linked to underlying comorbidities, adverse presenting features, and poor outcomes. Urgent strategies are needed to improve the outcomes of these patients.

Evaluation of the Use of Blood Products in ICU Hospitalized COVID-19 Patients

(1) Background: The COVID-19 pandemic tested the public health system’s readiness for crises and highlighted the importance of knowing the demand for blood products and the maintenance of the blood supply chain. The aim of this study was to evaluate blood product usage in a series of patients that were hospitalized due to COVID-19 and to analyze their demographics and clinical characteristics. (2) Methods: In this retrospective cohort study, we analyzed data from transfused COVID-19 patients that were treated in the University Hospital Medical Center Bezanijska Kosa in Belgrade, Serbia during the second wave of the epidemic. (3) Results: This study included 90 patients. The median age of the patients was 72 (range 23–95) years. The median time of hospitalization was 23 days (range 3–73 days). In intensive care units (ICUs) the median time of hospitalization was 9 days (range 0–73). One or more comorbidities were observed in 86 individuals (95.6%). The total number of transfused red blood cell concetrates (RBC) was 304 (139 in ICU, 165 in other wards), with a mean of 3 units/patient (range 1–14). Comorbidities, severity of illness and hospital duration in the ICU were statistically significant predictors of higher RBC use. (4) Conclusion: Knowledge of the transfusion profile of COVID-19 patients allowed better management of the hospital’s blood stocks during the COVID-19 pandemic.

Development and Validation of a Multivariable Predictive Model for Mortality of COVID-19 Patients Demanding High Oxygen Flow at Admission to ICU: AIDA Score.

INTRODUCTION: Risk stratification is an important aspect of COVID-19 management, especially in patients admitted to ICU as it can provide more useful consumption of health resources, as well as prioritize critical care services in situations of overwhelming number of patients. MATERIALS AND METHODS: A multivariable predictive model for mortality was developed using data solely from a derivation cohort of 160 COVID-19 patients with moderate to severe ARDS admitted to ICU. The regression coefficients from the final multivariate model of the derivation study were used to assign points for the risk model, consisted of all significant variables from the multivariate analysis and age as a known risk factor for COVID-19 patient mortality. The newly developed AIDA score was arrived at by assigning 5 points for serum albumin and 1 point for IL-6, D dimer, and age. The score was further validated on a cohort of 304 patients admitted to ICU due to the severe form of COVID-19. RESULTS: The study population included 160 COVID-19 patients admitted to ICU in the derivation and 304 in the validation cohort. The mean patient age was 66.7 years (range, 20-93 years), with 68.1% men and 31.9% women. Most patients (76.8%) had comorbidities with hypertension (67.7%), diabetes (31.7), and coronary artery disease (19.3) as the most frequent. A total of 316 patients (68.3%) were treated with mechanical ventilation. Ninety-six (60.0%) in the derivation cohort and 221 (72.7%) patients in the validation cohort had a lethal outcome. The population was divided into the following risk categories for mortality based on the risk model score: low risk (score 0-1) and at-risk (score > 1). In addition, patients were considered at high risk with a risk score > 2. By applying the risk model to the validation cohort (n = 304), the positive predictive value was 78.8% (95% CI 75.5% to 81.8%); the negative predictive value was 46.6% (95% CI 37.3% to 56.2%); the sensitivity was 82.4% (95% CI 76.7% to 87.1%), and the specificity was 41.0% (95% CI 30.3% to 52.3%). The C statistic was 0.863 (95% CI 0.805-0.921) and 0.665 (95% CI 0.598-0.732) in the derivation and validation cohorts, respectively, indicating a high discriminative value of the proposed score. CONCLUSION: In the present study, AIDA score showed a valuable significance in estimating the mortality risk in patients with the severe form of COVID-19 disease at admission to ICU. Further external validation on a larger group of patients is needed to provide more insights into the utility of this score in everyday practice.

Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy.

INTRODUCTION: Mortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality. METHODS: We performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients. RESULTS: The mean patient age was 65.6 years (range, 29-92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6-18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12-28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis. CONCLUSION: In the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality.