Abstract Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

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Exertional heat stress (EHS) disturbs the integrity of the gastrointestinal tract leading to endotoxaemia and cytokinaemia, which have symptomatic and health implications. This study aimed to determine the effects of carbohydrate and protein intake during EHS on gastrointestinal integrity, symptoms, and systemic responses. Eleven (male, n = 6; female, n = 5) endurance runners completed 2 h of running at 60% maximal oxygen uptake in 35 °C ambient temperature on 3 occasions in randomised order, consuming water (WATER), 15 g glucose (GLUC), or energy-matched whey protein hydrolysate (WPH) before and every 20 min during EHS. Rectal temperature and gastrointestinal symptoms were recorded every 10 min during EHS. Blood was collected pre- and post-EHS, and during recovery to determine plasma concentrations of intestinal fatty-acid binding protein (I-FABP) as a marker of intestinal epithelial injury, cortisol, endotoxin, and inflammatory cytokines. Urinary lactulose/l-rhamnose ratio was used to measure small intestine permeability. Compared with WATER, GLUC, and WPH ameliorated EHS associated intestinal epithelial injury (I-FABP: 897 ± 478 pg·mL vs. 123 ± 197 pg·mL and 82 ± 156 pg·mL, respectively, p < 0.001) and small intestine permeability (lactulose/l-rhamnose ratio: 0.034 ± 0.014 vs. 0.017 ± 0.005 and 0.008 ± 0.002, respectively, p = 0.001). Endotoxaemia was observed post-EHS in all trials (10.2 pg·mL, p = 0.001). Post-EHS anti-endotoxin antibodies were higher (p < 0.01) and cortisol and interleukin-6 lower (p < 0.05) on GLUC than WATER only. Total and upper gastrointestinal symptoms were greater on WPH, compared with GLUC and WATER (p < 0.05), in response to EHS. In conclusion, carbohydrate and protein intake during EHS ameliorates intestinal injury and permeability. Carbohydrate also supports endotoxin clearance and reduces stress markers, while protein appears to increase gastrointestinal symptoms, suggesting that carbohydrate is a more appropriate option.

Exertional-heat stress induces a thermoregulatory strain that subsequently injures the intestinal epithelium, reduces endotoxin clearance capacity, promotes greater cytokinaemia, and development of gastrointestinal symptoms.

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Debilitating gastrointestinal symptoms is a common feature of endurance running and may be exacerbated by and/or limit the ability to tolerate carbohydrate intake during exercise. The study aimed to determine whether two weeks of repetitive gut-challenge during running can reduce exercise-associated gastrointestinal symptoms and carbohydrate malabsorption. Endurance runners (n=18) performed an initial gut-challenge trial (GC1) comprising 2-hour running exercise at 60% VO (steady state) while consuming a formulated gel-disk containing 30 g carbohydrates (2:1 glucose-fructose, 10% w/v) every 20 minutes, followed by a 1-hour running effort bout. Gastrointestinal symptoms, feeding tolerance, and breath hydrogen (H ) were determined along the gut-challenge trial. After GC1, participants were randomly assigned to a blinded carbohydrate (CHO, 90 gCHO hour ) or placebo (PLA, 0 gCHO hour ) gut-training group. This comprised of consuming the group-specific feeding intervention during 1-hour running exercise at 60% VO equivalent, daily over a period of two weeks. Participants then repeated the gut-challenge trial (GC2). In GC2, a reduced gut discomfort (P=.012), total (P=.009), upper- (P=.015), and lower-gastrointestinal (P=.008) symptoms, and nausea (P=.05) were observed on CHO, but not PLA. Feeding tolerance did not differ between GC1 and GC2 on CHO and PLA. H peak was attenuated in GC2 (6±3 ppm) compared to GC1 (13±6 ppm) on CHO (P=.004), but not on PLA (GC1 11±7 ppm, and GC2 10±10 ppm). The effort bout distance was greater in GC2 (12.3±1.3 km) compared with GC1 (11.7±1.5 km) on CHO (P=.035) only. Two weeks of repetitive gut-challenge improve gastrointestinal symptoms and reduce carbohydrate malabsorption during endurance running, which may have performance implications.

The study aimed to determine the effects of mild exertional heat stress on intestinal injury, permeability, gastrointestinal symptoms, and systemic endotoxin and cytokine responses. Ten endurance runners completed 2 h of running at 60% V̇O in warm (WARM: 30°C) and temperate (TEMP: 22°C) ambient conditions. Rectal temperature (T) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid-binding protein (I-FABP) and cortisol concentrations, and systemic endotoxin and inflammatory cytokine profiles. Urinary lactulose:L-rhamnose ratio (L/R) was used to measure small intestine permeability. Compared with TEMP, WARM significantly increased T from 50 min onwards (38.1±0.3°C vs. 38.4±0.5°C, respectively; p<0.01), gastrointestinal symptoms (p=0.017), post-exercise plasma cortisol (26% vs. 59%, respectively; p<0.001) and I-FABP (127% vs. 184%, respectively; p<0.001) concentrations. Circulatory anti-endotoxin antibodies increased post-exercise (p<0.001) on WARM (20%) and TEMP (28%). No differences were observed for plasma endotoxin concentration (6% vs. 5% increase, respectively) or small intestine permeability (L/R 0.026±0.010 and 0.025±0.015, respectively). Both pro- and anti-inflammatory cytokines increased post-exercise, with inflammatory response cytokines TNF-α (p=0.015) and IL-8 (p=0.044), and compensatory anti-inflammatory cytokines IL-10 (p=0.065), and IL-1ra higher on WARM than TEMP. Findings suggest that exposure to warm ambient conditions during prolonged submaximal running induces transient intestinal epithelial injury, increases gastrointestinal symptoms, and promotes greater perturbations to the systemic cytokine profile compared to running in temperate conditions.

The evidence identified suggests that mealtime assistance provided to hospitalised older patients (≥65 years) leads to a statistically significant increase in energy and protein intake. For many patients, this increase in both energy and protein intake will be clinically significant, reducing the gap between requirements and actual intake.