Much of the underlying disease mechanisms of COVID-19 infection is yet to be learned. It has become clear, that COVID-19 has profound impact on the haematological system, including white blood cell morphology, but systematic reports are lacking. In the present Morphological changes in COVID-19 study, we evaluated haematological and morphological parameters for patients with COVID-19 and patients with suspected COVID-19 infection but negative real-time polymerase chain reaction (RT-PCR) admitted to Kolding Hospital and Odense University hospital between the 10 th of March and the 16 th of April 2020. COVID-19 positive patients were matched for age and gender with non-COVID-19 patients. We found COVID-19 patients to have lower white blood cell, neutrophil, lymphocyte, monocyte, and platelet count compared to non-COVID-19 patients. Mean platelet volume, platelet distribution width, and platelet large cell ratio was conversely higher in COVID-19 patients. In terms of red blood cell indices, only minor differences were found when comparing COVID-19 to non-COVID-19 patients. Patients with severe COVID-19 disease had higher immature granulocyte count and lower neutrophil and platelet count than patients with non-severe disease courses. The majority of non-COVID-19 patients had a normal morphological examination (83.3%), compared to 14.8% of COVID-19 patients. Hypogranulated neutrophils were more frequent in COVID-19 patients, but no significant differences were found for neutrophil hypergranulation, neutrophil vacuolation, plasmatoid cells, plasma cells, giant platelets, band neutrophils, or hypersegmented neutrophils. In conclusion, several haematological morphological abnormalities are more frequent in patients with COVID-19 disease, there are indications of platelets playing a fundamental role in the pathophysiology of the disease.

Background Severe acute respiratory syndrome coronavirus 2 (COVID-19) poses substantial challenges for health care systems. With a vastly expanding amount of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease. Content PubMed (Medline), Scopus, and Web of Science were searched until the 22nd of March 2020 for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesised and we conducted random effects meta-analysis and estimated mean difference (MD) and standard mean difference at biomarker level for disease severity. Risk of bias and applicability concern was evaluated using the Quality Assessment of Diagnostic Accuracy Studies -2. Summary 45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous, but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD 1.28 x 109/L), neutrophil count (MD 1.49 x 109/L), C-reactive protein (MD 49.2 mg/L), lactate dehydrogenase (MD 196 U/L), D-dimer (SMD 0.58), and aspartate aminotransferase (MD 8.5 U/L), all p < 0.001. Furthermore, low lymphocyte count (MD -0.32 x 109/L), platelet count (MD -22.4 x 109/L), and haemoglobin (MD -4.1 g/L), all p < 0.001, were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.

Studies on markers for bleeding risk among thrombocytopenic cancer patients are lacking. This prospective observational cohort study investigated whether platelet parameters and a standardised bleeding questionnaire predicted bleeding or prophylactic platelet transfusions in patients with cancer and thrombocytopenia. Admitted adult patients with cancer and platelet count <80 × 10(9)/L were enrolled, but excluded if they experienced surgery or trauma within 7 days or platelet transfusion within 14 days. Patients were interviewed, blood samples collected and, subsequently, spontaneous bleeding and prophylactic platelet transfusion within 30 days were registered. Of 197 patients enrolled, 56 (28%) experienced bleeding. In multivariate analyses, predictors of bleeding were infection (adjusted odds ratio (OR) = 2.65 and 95% confidence interval (95% CI) 1.04-6.74); treatment with platelet inhibitors, heparin or warfarin OR = 2.34, 95% CI 1.23-4.48; urea nitrogen OR = 1.15, 95% CI 1.07-1.25; creatinine OR = 1.01, 95% CI 1.01-1.01; and haemoglobin OR = 0.62, 95% CI 0.41-0.93. Specific information regarding previous gastrointestinal bleeding OR = 3.33, 95% CI 1.19-9.34 and haematuria OR = 3.00, 95% CI 1.20-7.52 predicted bleeding whereas the standardised bleeding questionnaire did not. Prophylactic platelet transfusions were administered to 97 patients. Predictors of prophylactic platelet transfusions were: platelet count OR = 0.96, 95% CI 0.94-0.97; fibrinogen OR = 0.88, 95% CI 0.83-0.95; mean platelet volume OR = 0.69, 95% CI 0.49-0.97; platelet aggregometry with OR = 2.48, 95% CI 1.09-5.64 for collagen-induced platelet aggregation within the lowest quartile; and albumin OR = 1.07, 95% CI 1.01-1.15. In conclusion, except for immature platelet fraction (IPF), platelet parameters predicted prophylactic platelet transfusion but not bleeding. Bleeding risk factors were previous haematuria or gastrointestinal bleeding, infection, antiplatelet or anticoagulant treatment, high urea nitrogen, low haemoglobin or high creatinine.

No abstract

Background The epidermal growth factor receptor (EGFR) system is involved in cancer pathogenesis and serves as an important target for multiple cancer treatments. EGFR and its ligands epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF), betacellulin (BTC), amphiregulin (AREG) and transforming growth factor α (TGF-α) have potential applications as prognostic or predictive serological biomarkers in cancer. The aim was to establish EGFR and EGFR ligand reference intervals in healthy women. Methods EGFR and EGFR ligands were measured in serum from 419 healthy women aged 26–78 years. The need for age partitioned reference intervals was evaluated using Lahti’s method. EGFR and EGF were analyzed using ELISA assays, whereas HB-EGF, BTC, AREG and TGF-α were analyzed using the highly sensitive automated single molecule array (Simoa) enabling detection below the lower reference limit for all six biomarkers. Results Reference intervals for EGFR and the EGFR ligands were determined as the 2.5th and 97.5th percentiles. All six biomarkers were detectable in all serum samples. For EGFR, EGF, HB-EGF and TGF-α, reference intervals were established for women <55 years and for women >55 years, whilst common reference intervals were established for AREG and BTC including women aged 26–78 years. Conclusions Age specific reference intervals were determined for EGFR, EGF, HB-EGF, BTC, AREG and TGF-α.