Positive direct antiglobulin tests in cancer patients hospitalized with COVID-19

Background: A positive direct antiglobulin test (DAT) is frequently observed for patients suffering from COVID-19 but its interpretation in transfusion dependent patients such as patients with solid and haematological malignancies is complex and multi-factorial. Aims: • To identify the incidence of DAT positivity in cancer patients hospitalized with COVID-19. • To explore the significance of DAT positivity in those patients by comparing with the DAT-negative COVID-19 patients (control group). Methods: This was a cross-sectional study done in India where samples were obtained from 88 cancer patients with confirmed COVID- 19. All patients were hospitalized. No patient had received COVID-19 convalescent plasm. IAT was negative in all patients. DAT was performed using column agglutination technology, and samples that were DAT positive were further investigated using monospecific DAT facility. If the strength of DAT was 2+ or above with IgG then the elution was performed with an elution kit. The eluates were then tested with a commercial three-cell panel of RBCs to establish whether the IgG antibodies had any RBC antigen specificity. In case the DAT was positive for C3d, the cold agglutination titre was estimated. A chi-square test was used for discrete variables, and a student t-test or a Wilcoxon-Mann-Whitney test was used with p-values below 0.05 considered as significant. Results: There was no significant difference between the patients with positive DAT and patients with negative DAT (Table 1). DAT was positive in 32 of 88 (36.36%) patients. Of the 32 cases, 28 (87.5%) were positive for IgG only, one (3.13%) was positive for both IgG and complement, and three (9.38%) were positive for C3d.More than 2+ agglutination was seen in 6 (18.8%) patients. Out for those six cases two were positive for C3d only (4+) with a cold agglutination titre of 2048. None of the eluted samples in rest of the four cases with IgG reactivity showed specificity for RBC antigens in the three-cell panel. Total bilirubin and LDH values were not different between two groups which suggest that the anaemia in DAT-positive group was not due to haemolysis rather it could be associated with severity of disease. The increase morality that was observed in DAT-positive group might be explained similarly. Summary/Conclusions: Results of this study show that a high percentage of cancer patients with COVID-19 are DAT positive, but majority of these patients do not have any evidence of haemolysis and do not require more blood transfusion compared to others. The clinical implications of this high DAT positivity in COVID-19 patients need further exploration. (Table Presented).

Elastocapillary network model of inhalation

The seemingly simple process of inhalation relies on a complex interplay between muscular contraction in the thorax, elastocapillary interactions in individual lung branches, propagation of air between different connected branches, and overall air flow into the lungs. These processes occur over considerably different length and timescales;consequently, linking them to the biomechanical properties of the lungs, and quantifying how they together control the spatiotemporal features of inhalation, remains a challenge. We address this challenge by developing a computational model of the lungs as a hierarchical, branched network of connected liquid-lined flexible cylinders coupled to a viscoelastic thoracic cavity. Each branch opens at a rate and a pressure that is determined by input biomechanical parameters, enabling us to test the influence of changes in the mechanical properties of lung tissues and secretions on inhalation dynamics. By summing the dynamics of all the branches, we quantify the evolution of overall lung pressure and volume during inhalation, reproducing the shape of measured breathing curves. Using this model, we demonstrate how changes in lung muscle contraction, mucus viscosity, and surface tension, and airway wall stiffness - characteristic of many respiratory diseases, including those arising from COVID-19, cystic fibrosis, chronic obstructive pulmonary disease, asthma, and emphysema - drastically alter inhaled lung capacity and breathing duration. Our work, therefore, helps to identify the key factors that control breathing dynamics and provides a way to quantify how disease-induced changes in these factors lead to respiratory distress. © 2020 authors. Published by the American Physical Society.