Analyse von Differentialblutbildern bei Patienten mit COVID-19-Erkrankung

COVID-19 is a new human infectious disease caused by the novel coronavirus SARS-CoV-2, that was first detected in Wuhan, the capital of Hubei Province in the People's Republic of China, in late December 2019. The disease has since spread worldwide and was officially declared a pandemic by the World Health Organization on March 11, 2020. The clinical presentation of COVID-19 is variable ranging from mild symptoms to severe illness. While COVID-19 predominantly affects the lungs, it is not limited to respiratory manifestations and has the potential to affect numerous organs including the hematopoietic system. Critically ill patients show signs of a dysregulated immune response and systemic hyperinflammation resulting in a hypercoagulable state with an increased tendency to develop thromboembolic complications. The most prevalent hematological findings associated with poor outcomes in patients with COVID-19 include neutrophilia, lymphopenia and thrombocytopenia. In this study we aimed to investigate the diagnostic and prognostic value of the hematological and hematopoietic abnormalities observed in a complete blood count and the peripheral blood smear. 20 laboratory-confirmed COVID-19-patients, that were hospitalized in the University Clinic of Marburg between March 19, 2020 and June 17, 2020 were included in the study cohort. For comparison 22 patients, that were admitted to the hospital over the same period of time with symptoms strongly suggestive of COVID-19 but negative pharyngeal swab tests, were studied as controls. Severe illness is designated when a patient required treatment on intensive care units. If no admission to the intensive care unit occurred during the hospital stay the course of the disease was defined as mild. The complete blood count was performed and evaluated using an automated analyzer. In addition, peripheral smear samples were prepared with a blood sample taken from an EDTA tube and examined microscopically. For statistical evaluation the parameters of the complete blood count were expressed as median and compared with the Mann-Whitney test. To examine the occurrence of morphological abnormalities the Fisher’s exact test was used. On admission, most COVID-19-patients presented with fever, dyspnea or cough and abnormalities in the chest computed tomographic images consistent with viral pneumonia were detected among all COVID-19-patients. Median length of hospital stay was 31.4 days and 15 out of the 20 hospitalized COVID-19-patients showed severe disease and were admitted to the intensive care unit. The complete blood count of COVID-19-patientes on admission revealed anemia, neutrophilia and leukocytosis. In addition, the median absolute count of monocytes and non-atypical lymphocytes were significantly lower in severe COVID-19-patients compared with COVID-19-patients showing mild disease. In peripheral blood films COVID-19-patients showed pronounced leukoerythroblastic features as well as variety of dysplastic changes in neutrophil granulocytes including pseudo-Pelger cells and unsegmented or ring-shaped nuclei. Furthermore, the blood film examination revealed an increased number of hypogranular neutrophils, that were presented more frequently by COVID-19-patientes compared to the control-group. Interestingly, this hypogranulation was found to disappear over time with more than half of the affected COVID-19-patients showing a normalization of the cytoplasmatic granularity during the hospitalization. Moreover, the peripheral blood smears of COVID-19-patients were characterized by vacuolated monocytes and a highly pleomorphic atypical lymphocyte population including large granular lymphocytes. An increased number of giant platelets, that were found more frequently in COVID-19-patients than in the control-group, complement the morphologic anomalies in all three hematologic lineages. In this study we were able to confirm that the COVID-19 is associated with a variety of characteristic hematological alterations. Particularly the absolute counts of monocytes and non-atypical lymphocytes were found to significantly correlate with disease severity. Given the prognostic value of these hematologic abnormalities, the evaluation of the full blood count may help to ensure risk stratification and effective management of COVID-19-patients. Our morphologic observations revealed hematologic multi-lineage changes and indicated serious perturbation of the entire hematopoiesis due to the SARS-CoV-2-infection. Especially the hypogranulation of the neutrophil granulocytes as well as the presence of numerous giant platelets emerged as COVID-19-specific dysplastic changes in peripheral blood films. Therefore, complementary morphologic analysis might be helpful in the diagnosis of COVID-19-patientes. Further studies are necessary to assess the mechanisms of interaction between SARS-CoV-2 and the hematopoietic system. Better understanding of the pathophysiology of the disease may lead to better treatment options and eventually result in a decrease of COVID-19-associated mortality.