Background
Emerging studies indicate that some COVID-19 patients suffer from persistent symptoms including breathlessness and chronic fatigue; however the long-term immune response in these patients presently remains ill-defined.
Methods
Here we describe the phenotypic and functional characteristics of B and T cells in hospitalised COVID-19 patients during acute disease and at 3-6 months of convalescence.
Findings
We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic programme evident in CD8
+
T cells as well as elevated production of type-1 cytokines and IL-17. Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to toll-like receptor activation, skewed towards a pro-inflammatory phenotype. Whereas the frequency of IL-6
+
B cells was restored in convalescent patients irrespective of clinical outcome, recovery of IL-10
+
B cells was associated with resolution of lung pathology.
Conclusions
Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with one subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalisation with COVID-19 could impact longer term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients.
Funding
Provided by UKRI, Lister Institute of Preventative Medicine, The Wellcome Trust, The Kennedy Trust for Rheumatology Research and 3M Global Giving.
Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare disease characterized by attacks of edema, known to impact quality of life (QoL). This study investigates the burden of HAE in Swedish patients, both children and adults. We used a retrospective registry study of Swedish patients with HAE, captured by the Sweha-Reg census. Data were collected using a paper-based survey. Patients completed EuroQoL 5 Dimensions 5 Levels (EQ5D-5L) questionnaires for both the attack-free state (EQ5D today), and the last HAE attack (EQ5D attack). Questions related to patient's age and sex and other variables, such as attack location and severity, were included to better understand the burden of HAE. EQ5D-5L values were estimated for the two HAE disease states. Patient-reported sick leave was also analyzed. A total of 103 responses were analyzed from 139 surveys (74% response rate). One hundred one reported an EQ5D today score (mean, 0.825) and 78 reported an EQ5D attack score (mean, 0.512) with significant differences between the two states (p < 0.0001). This difference was observed for both mild (p < 0.05), moderate (p < 0.0001), and severe attacks (p < 0.0001). Attack frequency had a negative effect on EQ5D today. Patients with >30 attacks a year had a significantly lower EQ5D today score than those with less frequent attacks. Of 74 participants, 33 (44.6%) had been absent from work or school during the latest attack and, of those with a severe attack, 81% had been absent. HAE has a significant impact on QoL both during and between attacks and on absenteeism during attacks.
Dexamethasone (3-300 mumol/l) did not affect uptake of choline (1 mumol/l) by rat forebrain isolated nerve terminals (crude synaptosomal fraction). At concentrations which have been shown to increase choline uptake by rat superior cervical ganglion, dexamethasone had no effect on synaptosomal choline uptake at choline concentrations between 0.1 and 30 mumol/l, nor on choline uptake which had been partially inhibited either by hemicholinium-3 (0.1 mumol/l) or by reducing the NaCl concentration (0-140 mmol/l).
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