Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19.

Due to the molecular mechanisms of action of antidiabetic drugs, they are considered to be effective in the treatment of both COVID-19 and the post-COVID-19 syndromes. The aim of this study was to determine the effect of administering insulin and metformin on the mortality of patients with type 2 diabetes (T2DM) with symptomatic COVID-19 with the use of logistic regression models. The association between death and insulin and metformin was weak and could not be included in the multivariate model. However, the interaction of both drugs with other factors, including remdesivir and low-molecular-weight heparin (metformin), age and hsCRP (insulin), modulated the odds of death. These interactions hint at multifaceted (anti-/pro-) associations of both insulin and metformin with the odds of death, depending on the patient's characteristics. In the multivariate model, RDW-SD, adjusted with low-molecular-weight heparin treatment, age, sex and K+, was associated with mortality among patients with COVID-19 and T2DM. With a 15% increase in RDW-SD, the risk of death increased by 87.7%. This preliminary study provides the foundations for developing further, more personalized models to assess the risk of death in T2DM patients, as well as for identifying patients at an increased risk of death due to COVID-19.

Ebbing Strength, Fading Power: Unveiling the Impact of Persistent Fatigue on Muscle Performance in COVID-19 Survivors.

The total number of confirmed cases of COVID-19 caused by SARS-CoV-2 virus infection is over 621 million. Post-COVID-19 syndrome, also known as long COVID or long-haul COVID, refers to a persistent condition where individuals experience symptoms and health issues after the acute phase of COVID-19. The aim of this study was to assess the strength and fatigue of skeletal muscles in people recovered from COVID-19. A total of 94 individuals took part in this cross-sectional study, with 45 participants (referred to as the Post-COVID Cohort, PCC) and 49 healthy age-matched volunteers (Healthy Control Cohort, HCC). This research article uses the direct dynamometry method to provide a detailed analysis of post-COVID survivors' strength and power characteristics. The Biodex System 4 Pro was utilized to evaluate muscle strength characteristics during the fatigue test. The fatigue work in extensors and flexors was significantly higher in the PCC. The PCC also showed significantly less power in both extensors and flexors compared to the HCC. In conclusion, this study provides compelling evidence of the impact of post-COVID-19 fatigue on muscle performance, highlighting the importance of considering these effects in the rehabilitation and care of individuals recovering from the virus. PCC achieved lower muscle strength values than HCC.

Usefulness of the Veterans Health Administration COVID-19 (VACO) Index for Predicting Short-Term Mortality among Patients of the COLOS Study.

Advanced age is known to be a predictor with COVID-19 severity. Understanding of other disease progression factors may shorten the time from patient admission to applied treatment. The Veterans Health Administration COVID-19 (VACO index) was assumed to additionally anticipate clinical results of patients hospitalized with a proven infection caused by the SARS-CoV-2 virus. METHODS: The medical records of 2183 hospitalized patients were retrospectively analyzed. Patients were divided into four risk-of-death categories: low risk, medium risk, high-risk, and extreme risk depending on their VACO index calculation. RESULTS: Significant differences in the mortality at the hospital after three months of discharge and six months after discharge were noticed. For the patients in the extreme-risk group, mortality reached 37.42%, 62.81%, and 78.44% for in-hospital, three months of discharge, and six months of discharge, respectively. The mortality marked as high risk reached 20.38%, 37.19%, and 58.77%. Moreover, the secondary outcomes analysis acknowledged that patients classified as extreme risk were more likely to suffer from cardiogenic shock, myocardial infarction, myocardial injury, stroke, pneumonia, acute kidney injury, and acute liver dysfunction. Patients at moderate risk were more often admitted to ICU when compared to other patients. CONCLUSIONS: The usage of the VACO index, combined with an appropriate well-defined medical interview and past medical history, tends to be a helpful instrument in order to predict short-term mortality and disease progression based on previous medical records.

Effect of COVID-19 on Musculoskeletal Performance in Gait and the Timed-Up and Go Test.

INTRODUCTION: The total number of confirmed cases of COVID-19 caused by the SARS-CoV-2 virus infection is over 621 million in the world. In approximately 63% of cases, the patient still experiences persistent symptoms 30 days after the onset of symptoms or hospitalisation, and 45.9% of patients have experienced or will experience symptoms for at least three months. Despite the prevalence of chronic symptoms and pathological changes that may affect gait and functional mobility in people with a history of COVID-19, there are few publications investigating the impact of these abnormalities. This study aims to determine the long-term effects of COVID-19 on gait and the Timed-Up and Go Task. MATERIAL AND METHODS: A total of 30 individuals took part in the experiment. The subjects in the study group were infected with the COVID-19 virus and required hospital treatment. Prior to the study, the subjects had no chronic diseases or other conditions affecting the musculoskeletal system. The non-infected by COVID-19 group was a healthy population with no history of COVID-19 disease. The study used the inertial system wireless motion analysis system based on 15 inertial sensors (inertial measurement units, IMUs). IMU sensors were placed on the following body segments: head, sternum, middle and lower spine, shoulder, arm, forearm, hand, shank, for the left and right limb. Movement task reports generated from the recording were created using myoRESEARCH 3.10. The subjects in the study group were asked to perform a movement task test-the Timed-Up and Go Test (TUG): sit-to-stand, walk (3 m) without change in direction, walk termination, and stand-to-sit. RESULTS: It took 46% longer for those infected by COVID-19 (participants) to complete the entire movement task compared to those in the not-infected by COVID-19 group. Sit-to-Stand Time [s] was greater in the infected by COVID-19 group and was 2.1 ± 0.7. Mean Walking Speed [m/s] was lower than in the not-infected by COVID-19 group and was 0.26 ± 0.07. Walking cadence [steps/min] was lower and was 21.2 ± 1.2. Infected by COVID-19 participants achieved a smaller anterior pelvic tilt angle (p < 0.001) and a smaller hip flexion angle (p = 0.025), with an increase in knee (p < 0.001) and ankle (p < 0.001) flexion angles. CONCLUSIONS: Individuals in the infected by COVID-19 group present changes in the ranges of motion and the time to complete the TUG task, despite the fact that at least eight weeks passed after hospital discharge.

Physical Activity Modifies the Severity of COVID-19 in Hospitalized Patients-Observational Study.

BACKGROUND AND AIM: Physical activity (PA) can modulate the immune response, but its impact on infectious disease severity is unknown. We assess if the PA level impacts the severity of COVID-19. METHODS: Prospective, cohort study for adults hospitalized due to COVID-19, who filled out the International Physical Activity Questionnaire (IPAQ). Disease severity was expressed as death, transfer to intensive care unit (ICU), oxygen therapy (OxTh), hospitalization length, complications, C-reactive protein, and procalcitonin level. RESULTS: Out of 326 individuals, 131 (57; 43.51% women) were analyzed: age: median-70; range: 20-95; BMI: mean-27.18 kg/m²; and SD: ±4.77. During hospitalization: 117 (83.31%) individuals recovered, nine (6.87%) were transferred to ICU, five (3.82%) died, and 83 (63.36%) needed OxTh. The median for the hospital stay was 11 (range: 3-49) for discharged patients, and mean hospitalization length was 14 (SD: ±5.8312) for deaths and 14.22 days (SD: ±6.92) for ICU-transferred patients. The median for MET-min/week was 660 (range: 0-19,200). Sufficient or high PA was found in recovered patients but insufficient PA was observed in dead or ICU-transferred patients (p = 0.03). The individuals with poor PA had a higher risk of death (HR = 2.63; ±95%CI 0.58-11.93; p = 0.037). OxTh was used more often in the less active individuals (p = 0.03). The principal component analysis confirmed a relationship between insufficient PA and an unfavorable course of the disease. CONCLUSION: A higher level of PA is associated with a milder course of COVID-19.

Dysnatremia in COVID-19 Patients-An Analysis of the COLOS Study.

BACKGROUND: Sodium imbalance is one of the most common electrolyte disturbances encountered in the medical practice, and it may present with either hyponatremia or hypernatremia. Both sodium abnormalities are related with unfavorable outcomes. OBJECTIVE: Elucidation of the prevalence of dysnatremia among COVID-19 patients and its impact on 30- and 90-day mortality and need for ICU admission was the goal. DESIGN AND PARTICIPANTS: A single-center, retrospective, observational study was conducted. A total of 2026 adult, SARS-CoV-2 positive patients, admitted to Wroclaw University Hospital between 02.2020 and 06.2021, were included. On admission, patients were divided into groups: normonatremic (N), hyponatremic (L), and hypernatremic (H). Acquired data was processed, and Cox hazards regression and logistic regression were implemented. KEY RESULTS: Hyponatremia on admission occurred in 17.47% (n = 354) of patients and hypernatremia occurred in 5.03% (n = 102). Dysnatremic patients presented with more comorbidities, used more drugs, and were statistically more often admitted to the ICU. Level of consciousness was the strongest predictor of ICU admission (OR = 1.21, CI: 1.16-1.27, p < 0.001). Thirty-day mortality was significantly higher in both the L and H groups (28.52%, p = 0.0001 and 47.95%, p < 0.0001, respectively), in comparison to 17.67% in the N group. Ninety-day mortality showed a similar trend in all study groups: 34.37% in the L group (p = 0.0001), 60.27% (p < 0.0001) in the H group, and 23.32% in the N group. In multivariable analyses, hypo- and hypernatremia were found to be independent predictors of 30- and 90-day mortality. CONCLUSIONS: Both hypo- and hypernatremia are strong predictors of mortality and disease severity in COVID-19 patients. Extraordinary care should be taken when dealing with hypernatremic, COVID-positive patients, as this group exhibits the highest mortality rates.

The Usefulness of the COVID-GRAM Score in Predicting the Outcomes of Study Population with COVID-19.

BACKGROUND: The COVID-GRAM is a clinical risk rating score for predicting the prognosis of hospitalized COVID-19 infected patients. AIM: Our study aimed to evaluate the use of the COVID-GRAM score in patients with COVID-19 based on the data from the COronavirus in the LOwer Silesia (COLOS) registry. MATERIAL AND METHODS: The study group (834 patients of Caucasian patients) was retrospectively divided into three arms according to the risk achieved on the COVID-GRAM score calculated at the time of hospital admission (between February 2020 and July 2021): low, medium, and high risk. The Omnibus chi-square test, Fisher test, and Welch ANOVA were used in the statistical analysis. Post-hoc analysis for continuous variables was performed using Tukey's correction with the Games-Howell test. Additionally, the ROC analysis was performed over time using inverse probability of censorship (IPCW) estimation. The GRAM-COVID score was estimated from the time-dependent area under the curve (AUC). RESULTS: Most patients (65%) had a low risk of complications on the COVID-GRAM scale. There were 113 patients in the high-risk group (13%). In the medium- and high-risk groups, comorbidities occurred statistically significantly more often, e.g., hypertension, diabetes, atrial fibrillation and flutter, heart failure, valvular disease, chronic kidney disease, and obstructive pulmonary disease (COPD), compared to low-risk tier subjects. These individuals were also patients with a higher incidence of neurological and cardiac complications in the past. Low saturation of oxygen values on admission, changes in C-reactive protein, leukocytosis, hyperglycemia, and procalcitonin level were associated with an increased risk of death during hospitalization. The troponin level was an independent mortality factor. A change from low to medium category reduced the overall survival probability by more than 8 times and from low to high by 25 times. The factor with the strongest impact on survival was the absence of other diseases. The medium-risk patient group was more likely to require dialysis during hospitalization. The need for antibiotics was more significant in the high-risk group on the GRAM score. CONCLUSION: The COVID-GRAM score corresponds well with total mortality. The factor with the strongest impact on survival was the absence of other diseases. The worst prognosis was for patients who were unconscious during admission. Patients with higher COVID-GRAM score were significantly less likely to return to full health during follow-up. There is a continuing need to develop reliable, easy-to-adopt tools for stratifying the course of SARS-CoV-2 infection.

The Usefulness of the C2HEST Risk Score in Predicting Clinical Outcomes among Hospitalized Subjects with COVID-19 and Coronary Artery Disease.

BACKGROUND: Even though coronary artery disease (CAD) is considered an independent risk factor of an unfavorable outcome of SARS-CoV-2-infection, the clinical course of COVID-19 in subjects with CAD is heterogeneous, ranging from clinically asymptomatic to fatal cases. Since the individual C2HEST components are similar to the COVID-19 risk factors, we evaluated its predictive value in CAD subjects. MATERIALS AND METHODS: In total, 2183 patients hospitalized due to confirmed COVID-19 were enrolled onto this study consecutively. Based on past medical history, subjects were assigned to one of two of the study arms (CAD vs. non-CAD) and allocated to different risk strata, based on the C2HEST score. RESULTS: The CAD cohort included 228 subjects, while the non-CAD cohort consisted of 1956 patients. In-hospital, 3-month and 6-month mortality was highest in the high-risk C2HEST stratum in the CAD cohort, reaching 43.06%, 56.25% and 65.89%, respectively, whereas in the non-CAD cohort in the high-risk stratum, it reached: 26.92%, 50.77% and 64.55%. Significant differences in mortality between the C2HEST stratum in the CAD arm were observed in post hoc analysis only for medium- vs. high-risk strata. The C2HEST score in the CAD cohort could predict hypovolemic shock, pneumonia and acute heart failure during hospitalization, whereas in the non-CAD cohort, it could predict cardiovascular events (myocardial injury, acute heart failure, myocardial infract, carcinogenic shock), pneumonia, acute liver dysfunction and renal injury as well as bleedings. CONCLUSIONS: The C2HEST score is a simple, easy-to-apply tool which might be useful in risk stratification, preferably in non-CAD subjects admitted to hospital due to COVID-19.

Liver Function Tests in COVID-19: Assessment of the Actual Prognostic Value.

Deviations in laboratory tests assessing liver function in patients with COVID-19 are frequently observed. Their importance and pathogenesis are still debated. In our retrospective study, we analyzed liver-related parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), albumin, comorbidities and other selected potential risk factors in patients admitted with SARS-CoV-2 infection to assess their prognostic value for intensive care unit admission, mechanical ventilation necessity and mortality. We compared the prognostic effectiveness of these parameters separately and in pairs to the neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of in-hospital mortality, using the Akaike Information Criterion (AIC). Data were collected from 2109 included patients. We created models using a sample with complete laboratory tests n = 401 and then applied them to the whole studied group excluding patients with missing singular variables. We estimated that albumin may be a better predictor of the COVID-19-severity course compared to NLR, irrespective of comorbidities (p < 0.001). Additionally, we determined that hypoalbuminemia in combination with AST (OR 1.003, p = 0.008) or TBIL (OR 1.657, p = 0.001) creates excellent prediction models for in-hospital mortality. In conclusion, the early evaluation of albumin levels and liver-related parameters may be indispensable tools for the early assessment of the clinical course of patients with COVID-19.

Usefulness of C2HEST Score in Predicting Clinical Outcomes of COVID-19 in Heart Failure and Non-Heart-Failure Cohorts.

Background: Patients with heart failure represent a vulnerable population for COVID-19 and are prone to having worse prognoses and higher fatality rates. Still, the clinical course of the infection is dynamic, and complication occurrence in particular in patients with heart failure is fairly unpredictable. Considering that individual components of the C2HEST (C2: Coronary Artery Diseases (CAD)/Chronic obstructive pulmonary disease (COPD); H: Hypertension; E: Elderly (Age ≥ 75); S: Systolic HF; T: Thyroid disease) are parallel to COVID-19 mortality risk factors, we evaluate the predictive value of C2HEST score in patients with heart failure (HF) Material and Methods: The retrospective medical data analysis of 2184 COVID-19 patients hospitalized in the University Hospital in Wroclaw between February 2020 and June 2021 was the basis of the study. The measured outcomes included: in-hospital mortality, 3-month and 6-month all-cause-mortality, non-fatal end of hospitalization, and adverse in-hospital clinical events. Results: The heart failure cohort consists of 255 patients, while 1929 patients were assigned to the non-HF cohort. The in-hospital, 3-month, and 6-month mortality rates were highest in the HF cohort high-risk C2HEST stratum, reaching 38.61%, 53.96%, and 65.36%, respectively. In the non-HF cohort, in-hospital, 3-month, and 6-month mortalities were also highest in the high-risk C2HEST stratum and came to 26.39%, 52.78%, and 65.0%, respectively. An additional point in the C2HEST score increased the total death intensity in 10% of HF subjects (HR 1.100, 95% CI 0.968−1.250 p = 0.143) while in the non-HF cohort, the same value increased by 62.3% (HR 1.623, 95% CI 1.518−1.734 p < 0.0001). Conclusions: The C2HEST score risk in the HF cohort failed to show discriminatory performance in terms of mortality and other clinical adverse outcomes during hospitalization. C2HEST score in the non-HF cohort showed significantly better performance in terms of predicting in-hospital and 6-month mortality and other non-fatal clinical outcomes such as cardiovascular events (myocardial injury, acute heart failure, myocardial infarction, cardiogenic shock), pneumonia, sepsis, and acute renal injury.

Sex-Dependent Differences in Predictive Value of the C2HEST Score in Subjects with COVID-19-A Secondary Analysis of the COLOS Study.

Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C2HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C2HEST score result. The measured outcomes included: in-hospital-mortality, three-month- and six-month-all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C2HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C2HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C2HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C2HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes.

Usefulness of the C2HEST Score in Predicting the Clinical Outcomes of COVID-19 in Diabetic and Non-Diabetic Cohorts.

BACKGROUND: Diabetes mellitus is among the most frequent comorbidities worsening COVID-19 outcome. Nevertheless, there are no data regarding the optimal risk stratification of patients with diabetes and COVID-19. Since individual C2HEST components reflect the comorbidities, we assumed that the score could predict COVID-19 outcomes. MATERIAL AND METHODS: A total of 2184 medical records of patients hospitalized for COVID-19 at the medical university center were analyzed, including 473 diabetic patients and 1666 patients without any glucose or metabolic abnormalities. The variables of patients' baseline characteristics were retrieved to calculate the C2HEST score and subsequently the diabetic and non-diabetic subjects were assigned to the following categories: low-, medium- or high-risk. The measured outcomes included: in-hospital mortality; 3-month and 6-month all-cause mortality; non-fatal end of hospitalization (discharged home/sudden-deterioration/rehabilitation) and adverse in-hospital clinical events. RESULTS: A total of 194 deaths (41%) were reported in the diabetic cohort, including 115 in-hospital deaths (24.3%). The 3-month and 6-month in-hospital mortality was highest in the high-risk C2HEST stratum. The C2HEST score revealed to be more sensitive in non-diabetic-group. The estimated six-month survival probability for high-risk subjects reached 0.4 in both cohorts whereas for the low-risk group, the six-month survival probability was 0.7 in the diabetic vs. 0.85 in the non-diabetic group-levels which were maintained during whole observation period. In both cohorts, receiver operating characteristics revealed that C2HEST predicts the following: cardiogenic shock; acute heart failure; myocardial injury; and in-hospital acute kidney injury. CONCLUSIONS: We demonstrated the usefulness and performance of the C2HEST score in predicting the adverse COVID-19 outcomes in hospitalized diabetic subjects.

Can the Toll-like receptors 4 expression in peripheral blood mononuclear cells help assess the effectiveness of immunosuppression and the chance of a future good renal transplant function?

BACKGROUND: A small percentage of peripheral blood mononuclear cells (PBMCs) circulating during the kidney transplantation (KT) period remain in the blood long after transplantation. A part of the PBMCs penetrates the graft. AIM: To examine if the choice of immunosuppression may change TLR4ex and how TLR4ex affects the transplant function in the future. MATERIAL: The study population-143 transplanted patients (pts) (55 females, 88 males), mean age on recruitment day 50.33 ±â€¯12.8 years old, mean BMI 25.04 ±â€¯4.18. 41 pts. experienced delayed graft function (DGF+). 55 pts. were treated with cyclosporine A (CsA) and 88 with tacrolimus (Tac). All were treated with mofetil mycophenolate (MMF). The PBMCs acquisition and starting point of the follow-up (TLR-day) was at least one month after KT. METHOD: We investigated averaged mRNA expression of Toll-like receptors 4 (TLR4ex) in non-stimulated peripheral blood mononuclear cells with the use of real-time polymerase chain reaction. The KT pts. (All, Tac, CsA, DGF+) were divided by the respective median of their TLR4ex (lower: L-TLR4ex, higher: H-TLR4ex). Main clinical parameters and transplant biopsy files (if available) were assessed on TLR-day and post follow-up. RESULTS: We found that TLR4ex was reduced for a long time in patients who experienced delayed graft function. L-TLR4ex had a higher proportion of DGF+ patients, and patients treated with CsA but lower of those treated with Tac than in H-TLR4ex. The amplitude of changes in renal function parameters (ΔEGFR%/ΔsCr/ΔsCr%) was clearly less favorable for L-TLR4ex. Tacrolimus expressed a stabilizing effect. Both the positive vasculitis score and chronic graft nephropathy were more frequent in the L-TLR4ex group. On TLR-day an association of renal function and Tac concentration with TLR4ex was clear only in the tacrolimus population. The TLR4ex was lower in patients with a future deterioration of the graft function. CONCLUSION: In kidney transplant recipients the occurrence of DGF results in a long-term reduction of the averaged TLR4ex in PBMC. Tacrolimus exerts a clear, stabilizing, positive and dose-dependent effect on TLR4ex. An improvement in renal transplant function may be expected in KT patients with high TLR4ex. Evaluation of the averaged TLR4ex can be used to assess the efficacy of immunosuppression in the treatment with tacrolimus and to estimate the likelihood of deterioration in renal function.