RESUMO
BACKGROUND: This study aimed to determine the association between glycemic variability (GV) and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We prospectively analyzed data from inpatients (> 18 years old) with RT-PCR confirmed COVID-19 admitted between March 2020 and July 2021. All patients were hospitalized for more than 48 h and had at least six point-of-care capillary glucose tests obtained three times daily in the pre-prandial period during hospitalization. GV was measured using the glucose standard deviation (SD) and coefficient of variation (CV). ROC curve was adjusted to determine the SD and CV cutoff values associated with mortality (44.7 mg/dL and 27.5%, respectively); values above these were considered indicative of high GV. Logistic regression models were fitted to explore the association between GV and mortality in patients with and without diabetes. RESULTS: A total of 628 patients were stratified into SD < 44.7 mg/dL (n = 357) versus ≥ 44.7 mg/dL (n = 271) and CV < 27.5% (n = 318) versus ≥ 27.5% (n = 310) groups. After controlling for age, sex, presence of diabetes mellitus (DM) and cardiovascular disease, we found a significant association between high GV and mortality (odds ratio 2.99 [1.88-4.77] for SD and 2.43 [1.54-3.85] for CV; p values < 0.001). The mortality rate was higher with SD ≥ 44.7 mg/dL and CV ≥ 27.5% compared to that with SD < 44.7 mg/dL and CV < 27.5%, regardless of DM (p < 0.001 for all). CONCLUSION: High glycemic variability was independently associated with mortality in patients with and without DM, who were hospitalized with COVID-19.
RESUMO
Rationale: Myocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide. Objective: This histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury. Methods and Results: Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1ß, IL-4, IL-6, CD163, TNF-α, TGF-ß, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1ß, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis. Conclusions: The pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-ß and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.
