Klinisch-biochemische Biomarker der COVID-19 Erkrankung

The novel COVID-19 disease, caused by SARS-CoV-2, has been in scientific spotlight since November 2019. While strategies were taken to contain the pandemic, scientific interest is focused on improving the understanding of the pathogenicity of the virus, as well as the diagnostics and therapy of the new disease. The gold standard to diagnose the infection is via RT-PCR, which has been used at the beginning of the pandemic with a high false-negative rate. The aim of the present study was to provide support for RT-PCR based on laboratory parameters, as well as to provide risk stratification for pa-tients requiring intensive care or die based on the laboratory parameters on admission. A total of 46 patients were recruited between April 10th, 2020 and June 30st, 2020 at the University Hospital Marburg and clinical biochemical laboratory parameters were rec-orded on admission. By using RT-PCR tests from the nasopharynx, the patients were divided into nearly equal groups; patients with negative RT-PCR served as control group. For prognostic analyses, an additional subdivision was made into ICU and nor-mal ward patients, and deceased and survivors. Statistical analysis was performed us-ing the Mann-Whitney-U test and for dichotomous parameters, the Fisher-exact test. Different severity levels were classified using the NIH and WHO and compared using ANOVA. Cut-off values were established using ROC. Analysis of descriptive data revealed leading symptoms of cough, dyspnea and fever. While COVID-19 positives were characterized by prolonged length of stay and more frequent invasive ventilation, the groups were otherwise homogeneous in de-mographics, vital signs on admission, treatment strategies, and complications. As diagnostic biomarkers, ALT, Amyl, AST, CK, HDL, LDH and LIP could be quantified in our study, which were associated with similar results in the literature comparison. Based on the calculation of cut-off values, ALT, Amyl, AST, LDH and LIP were able to predict infection with SARS-CoV-2 with high sensitivity and specificity. While the de-scribed parameters were elevated in COVID-19 positives, only HDL was found to be decreased, probably due to its function as negative acute-phase protein. Etiologically, damage to the hepatic and pancreatic systems in COVID-19 patients seems to be causative, whereas cardiac damage can not only be explained by elevated CK and dyslipidemia by reduced HDL levels. The possible underlying pathomechanism may be due to an increased number of ACE2 receptors in the organs, which may infiltrate the SARS-CoV-2 virus and cause early damage. The routine laboratory parameters can support, but not replace, an assessment of COVID-19 disease when RT-PCR assays or rapid tests are pending. As prognostic biomarkers for a severe course with admission to intensive care, AST, urea and BUN, hs-TNI, NT-pro-BNP could be established. Prediction by ROC suc-ceeded with high sensitivity and specificity for all parameters, with NT-pro-BNP appear-ing most sensitive and the cardiac system as one of the first to indicate a severe out-come. Moreover, patients with different severity of the disease showed abnormalities in lipid profile and tP. Severely ill patients showed significantly higher cholesterol, HDL, LDL and tP levels than critically ill patients, while it was the other way around in triglyc-eride levels. In the present study, tBili and tP served as biomarkers for death from COVID-19 dis-ease, with tBili predicting death with good sensitivity and specificity. A prediction of death by tP was not possible due to low sensitivity and specificity. Possible causes for altered laboratory parameters in severe courses are increased cytokine levels in COVID-19 patients, which may cause hepatic, nephologic, cardiac, and lipid profile damage. Furthermore, due to hypoxic conditions, the release of pro-inflammatory cyto-kines may appear increased and trigger additional inflammatory responses. In the liter-ature comparison, further parameters could be important as prognostic parameters for a severe outcome as well as for death, which did not appear significant due to the small number of participants in the present study. From the findings of this study one can derive that special attention should be paid to the monitoring of these parameters, which allow risk stratification and, if necessary, triaging of severe cases. Optimization the individual treatments of patients can reduce the mortality of the disease.