Objectives Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 μg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm secondary to virally driven hyper-inflammation. However, increased pro-inflammatory cytokines are also seen in bacterial sepsis. This study aimed to assess the clinical utility of a cytokine panel in the assessment of COVID-19 with bacterial superinfections along with PCT and C-reactive protein (CRP). Methods The retrospective analysis included serum cytokines (interleukins; IL-1β, IL-6, IL-8 and tumour necrosis factor (TNFα)) measured using Ella™ (Bio-Techne, Oxford, UK) and PCT measured by Roche Cobas (Burgess Hill, UK) in patients admitted with COVID-19 between March 2020 and January 2021. Patients enrolled into COVID-19 clinical trials, treated with Remdesivir/IL-6 inhibitors were excluded. The cytokine data was compared between intensive care unit (ICU) patients, age matched non-ICU patients and healthy volunteers as well as ICU patients with high and normal PCT (≥0.5 vs. <0.5 μg/L). Results Cytokine concentrations and CRP were higher in COVID-19 patients (76; ICU & non-ICU) vs. healthy controls (n = 24), all p<0.0001. IL-6, IL-8, TNFα and were higher in ICU patients (n = 46) vs. non-ICU patients (n = 30) despite similar CRP. Among 46 ICU patients, the high PCT group (n = 26) had higher TNFα (p<0.01) and longer ICU stay (mean 47 vs. 25 days, p<0.05). There was no difference in CRP and blood/respiratory culture results between the groups. Conclusions Pro-inflammatory cytokines and PCT were higher in COVID-19 patients requiring ICU admission vs. non-ICU admissions despite no difference in CRP. Furthermore, TNFα was higher in those with high PCT and requiring longer ICU admission despite no difference in CRP or rate of bacterial superinfection.

Rationale Preconditioning is widely known to protect cardiomyocytes from reperfusion-induced cell death by activation of several pro-survival transductional pathways. The fact that preconditioning can be achieved remotely (Remote Ischaemic Preconditioning, RIPC) means that humoral factors are released from ischaemic limbs into the circulation carrying a pro-survival message. Exosomes are circulating nano-sized vesicles that mediate inter-cellular communication by carrying diverse proteins and RNA molecules. Here we studied the role of exosomes in mediating RIPC. Methods and Results We isolated exosomes from plasma of rats or humans subjected to RIPC. We characterised control or RIPC exosomes by electron microscopy, flow cytometry, western blot and nano-particle tracking analysis. Exosome concentration increased dramatically after RIPC in humans (from 3.5 ± 0.3x108 to 1.1 ± 0.3x109 exosomes/ml plasma; p < 0.01, n = 6), and administration of purified exosomes protected the heart from infarct in different settings including an in vivo rat model (vehicle: 47.4 ± 4.7; RIPC-Exosomes: 20.5 ± 3.9%Infarct/AAR; p < 0.01), ex vivo Langendorff (vehicle: 35.2 ± 3.3; RIPC-Exosomes: 21.2 ± 2.5% Infarct/AAR; p < 0.01), and in vitro hypoxia-reoxygenation of cardiomyocytes (43 ± 7% protection from death, p < 0.01). RIPC-Exosomes triggered rapid ERK phosphorylation (3.9 ± 0.1 fold over vehicle), and inhibition of upstream PI3K or MEK abolished ERK activation and inhibited cardioprotection. Conclusions We demonstrate that RIPC dramatically increases the concentration of exosomes in the circulation. Exosomes acutely activate pro-survival kinases that rapidly prepare the heart against ischemia-reperfusion injury. Exosomes represent a novel agent with the potential to be an endogenous, non-immunogenic and multi-signalling tool for cardioprotection.

AimsPublic Health England has identified that in COVID-19, death rates among ethnic minorities far exceeds that of the white population. While the increase in ethnic minorities is likely to be multifactorial, to date, no studies have looked to see whether values for routine clinical biochemistry parameters differ between ethnic minority and white individuals.MethodsBaseline biochemical data for 22 common tests from 311 SARS-CoV-2 positive patients presenting to hospital in April 2020 in whom ethnicity data were available was retrospectively collected and evaluated. Data comparisons between ethnic minority and white groups were made for all patient data and for the subset of patients subsequently admitted to intensive care.ResultsWhen all patient data were considered, the ethnic minority population had statistically significant higher concentrations of C reactive protein (CRP), aspartate aminotransferase and gamma-glutamyl transferase, while troponin T was higher in the white group. A greater proportion of ethnic minority patients were subsequently admitted to intensive care, but when the presenting biochemistry of this subset of patients was compared, no significant differences were observed between ethnic minority and white groups.ConclusionOur data show for the first time that routine biochemistry at hospital presentation in COVID-19 differs between ethnic minority and white groups. Among the markers identified, CRP was significantly higher in the ethnic minority group pointing towards an increased tendency for severe inflammation in this group.

Table 1 Advantages and disadvantages of walkie talkie use in health care settings Advantages Disadvantages Low cost Non-secure channel Easy to decontaminate per IPC guidance Miscommunication between multiple teams sharing the same channel Simple to operate Radio frequencies may be obstructed by hospital structures (e.g. lead lining within radiotherapy departments) Can be used while wearing PPE Specific communication approach required Does not rely on telecommunication infrastructure "One to many" communication provides instant access to the whole team