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Selected Publication:
Aziz, F.
Interplay of Influenza and SARS-CoV-2 Infections with Diabetes Mellitus and associated Comorbidities
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp. 218
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- Authors Med Uni Graz:
- Advisor:
- Sourij Harald
- von Lewinski Dirk
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- Abstract:
- Purpose Diabetes is considered a major risk factor for influenza and SARS-CoV-2 infections and their adverse outcomes. However, the underlying reasons that make diabetes a high-risk condition are unclear. Also, evidence on the performance of risk scores and biomarkers to predict the prognosis of seriously ill COVID-19 patients with diabetes is scarce. Moreover, the immunogenic response to COVID-19 vaccination and its impact on transient hyperglycaemia are yet to be investigated in people with diabetes. Methods The Austrian Health insurance (AHI) database (N = 504,184) was analyzed to investigate the impact of clinical characteristics, comorbidities, and age-adjusted Charlson Comorbidity Index (ACCI) on hospitalization and short-term mortality rates following influenza-related infection (IRI). The GÖG database (N = 40,602) was analyzed to investigate the impact of diabetes on intensive care unit (ICU) admission and in-hospital mortality following COVID-19 using the propensity score matching method. In-hospital mortality among ICU patients with COVID-19 (N = 5850) was predicted using global, Central European, and Austrian versions of SAPS 3. The COVID-19 in diabetes registry (N = 747) investigated the performance of various haematological, coagulation, inflammatory, hepatic, and cardiac biomarkers to predict in-hospital mortality. The COVAC-DM study (N = 160) investigated the impact of type 1 and type 2 diabetes and glycaemic control on antibody response after the first and second COVID-19 vaccinations. Also, short-term effects (2 days before and 3 days after the vaccination) of COVID-19 vaccination on glycaemia, insulin dosage, and carbohydrate intake were investigated in COVAC-DM participants on a continuous glucose monitoring system and insulin therapy (N = 74). Results In the AHI database, people with old age, comorbidities, and a higher ACCI were more likely to be hospitalized for IRI than those hospitalized for other reasons. The adjusted hazard ratio (aHR) for 90-day mortality increased with age (aHR: 3.00 to 7.15 for 50–59 to 80+ years), heart failure (aHR: 1.97, 95% confidence interval [CI]: 1.31–2.98), renal disease (aHR: 1.50, 95%CI: 1.05–2.14), and ACCI (aHR: 1.14, 95%CI: 1.08–1.19). In the GÖG database, diabetes was not significantly associated with in-hospital mortality (odds ratio [OR]: 1.08, 95%CI: 0.97–1.19) after propensity matching, while it was significantly associated with ICU admission (OR: 1.15, 95%CI: 1.04–1.28). In GÖG ICU patients, the SAPS 3 discrimination was 69% and was similar between diabetes and non-diabetes patients (70% vs. 68%, p = 0.193). The Brier score was >0.20 and calibration was inadequate (p <0.05 each) for all SAPS 3 versions in the entire, diabetes, and non-diabetes patients. In the COVID-19 registry, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. Of all biomarkers, NT-proBNP showed good discrimination (74%) and calibration (p = 0.302), while Troponin T showed good discrimination (81%) but poor calibration (p = 0.010). In the COVAC-DM study, antibody levels were similar (p >0.05) between type 1 diabetes, type 2 diabetes, well and insufficiently controlled glucose, and healthy controls. The antibody response decreased with increasing age (r = –0.45, p <0.001) and increased with increasing eGFR (r = 0.28, p = 0.001). In the COVAC-DM sub-study, time in range (p = 0.962, p = 0.704), time below range (p = 0.952, p = 0.704), and time above range (p = 0.941, p = 0.715) for glucose did not vary significantly around the vaccination period in type 1 and type 2 diabetes participants. Type 1 diabetes participants spent less average time in range (p = 0.045) and a higher time above range (p = 0.040) on days with a side effect score >0. The side effect score did not alter glycaemia in type 2 diabetes participants. The COVID-19 vaccination did not alter insulin dosage (p = 0.578, p = 0.346) and carbohydrate intake (p = 0.0