ObjectiveThe aims of this study were to describe community antibiotic prescribing patterns in individuals hospitalised with COVID-19, and to determine the association between experiencing diarrhoea, stratified by preadmission exposure to antibiotics, and mortality risk in this cohort.Design/methodsRetrospective study of the index presentations of 1153 adult patients with COVID-19, admitted between 1 March 2020 and 29 June 2020 in a South London NHS Trust. Data on patients’ medical history (presence of diarrhoea, antibiotic use in the previous 14 days, comorbidities); demographics (age, ethnicity, and body mass index); and blood test results were extracted. Time to event modelling was used to determine the risk of mortality for patients with diarrhoea and/or exposure to antibiotics.Results19.2% of the cohort reported diarrhoea on presentation; these patients tended to be younger, and were less likely to have recent exposure to antibiotics (unadjusted OR 0.64, 95% CI 0.42 to 0.97). 19.1% of the cohort had a course of antibiotics in the 2 weeks preceding admission; this was associated with dementia (unadjusted OR 2.92, 95% CI 1.14 to 7.49). After adjusting for confounders, neither diarrhoea nor recent antibiotic exposure was associated with increased mortality risk. However, the absence of diarrhoea in the presence of recent antibiotic exposure was associated with a 30% increased risk of mortality.ConclusionCommunity antibiotic use in patients with COVID-19, prior to hospitalisation, is relatively common, and absence of diarrhoea in antibiotic-exposed patients may be associated with increased risk of mortality. However, it is unclear whether this represents a causal physiological relationship or residual confounding.

ELS exposure (childhood adversity such as household dysfunction, abuse, or neglect) is an independent risk factor for adult-onset cardiovascular disease (CVD). ELS exposure is associated with increased circulating inflammatory markers in humans, as well as elevated aortic inflammatory monocytes in mice. The cellular sources and mechanisms of excessive cytokine production behind these findings are still poorly understood. We hypothesized that mice exposed to ELS, maternal separation with early weaning (MSEW), will have greater arterial stiffening and greater reactive aortic macrophages leading to a larger cytokine response when activated with LPS than normally reared (NR) mice. The MSEW model includes pups separated from the dam 4h/day (postnatal day (PD) 2 to PD5), 8h/day (PD6 to 16), and weaned at PD17. NR pups remain with the dams until weaning at PD21. Pulse wave velocity (PWV), a measure of aortic stiffness, determined at 6 wks of age found that MSEW mice had elevated PWV as compared to NR (NR: 1.2±0.08 mm/sec, MSEW: 2.1±0.04 mm/sec, p<0.0001, n=4,6). In the aorta, total F4/80+ macrophages as well as cells expressing activation markers CD86 and MHCII were elevated in 14 wk old MSEW mice (%F4/80+: NR:2.73±0.34, MSEW 5.04±0.56, p=0.004, n=7,5; %CD86: NR: 0.12±0.03, MSEW: 0.52±0.09, p=0.004, n=7,5; %MHCII: NR: 1.14±0.09, MSEW: 1.92±0.22, p=0.001, n=7,5). MSEW mice showed significantly elevated levels of macrophages (%CD11c-CD11b+F4/80+ of CD45+) in the spleen red pulp (NR: 1.09±0.04, MSEW: 1.28±0.07, P=0.03, n=14,10). However, expression of activation markers CD86 and MHCII as well as TNFα, IL-1b and IL6 in splenic macrophages from 14 wk old MSEW mice did not significantly differ between the MSEW and NR cohorts. Finally, we isolated splenic macrophages, stimulated with LPS (100 ng/mL) for 24 hrs and cytokine secretion measured by cytokine array. The qualitative array showed that the total supernatant of macrophage cultures from MSEW sample had greater IL1-ra, IL-16, G-CSF, CXCL10, macrophage inflammatory protein 1B and 2, and TNFα compared to cultures from NR samples. These results suggest that macrophages of MSEW mice are primed for inflammatory responses and may secrete intracellular cytokines compared to macrophages from NR mice. Elevated PWV is an early indicator for the development of CVD, seen as early as 6 wks in MSEW mice. Taken together these findings suggest a greater propensity for those who have experienced ELS to develop CVD. Future studies will aim to elucidate the role of the elevated macrophage derived cytokines in arterial stiffening. NIH R25 DK 112731, NIH R25 DK 115353, NIH T32 DK 116672 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vasopressin (VP) has been shown to enhance SARS-CoV-2 infectivity by enabling virus entry into cells via VP receptor 1B-mediated endocytosis after forming a complex with SARS-CoV-2 spike protein and angiotensin converting enzyme II (ACE2). While elevated VP circulating levels in response to hypoxemic shock or osmotic dysregulation in severe COVID-19 is expected, altered VP levels associated with the early immunological response to mild cases of COVID-19, may be more subtle. We hypothesized that if circulating VP is involved in facilitating viral infection, changes in VP levels may occur in the absence of changes in osmolality or cardiovascular decompensation. We also postulated that there may be a difference in immunological responses in natural infection vs vaccine-induced immunity. Immune responses of asymptomatic to moderately symptomatic non-hospitalized individuals (n=63) diagnosed with SARS-CoV-2 infection by PCR test were followed up to a month from onset of infection and compared to that of matched controls (n=130). The responses from those never vaccinated (n=67) were compared against those who received 2 doses of the Pfizer COVID-19 vaccine (n=103) and those who received a 3rd booster dose of vaccine (n=23). Blood specimens were analyzed for quantitative measurement of IgG targeted to the SARS-Cov-2 spike protein (Epitope Diagnostics, San Diego, CA) and circulating AVP (by radioimmunoassay). Elevated IgG against spike protein was evident at 14 and 28 days from infection. IgG levels in naturally infected individuals (87±14 U/ml) were surpassed by levels achieved in 2 dose vaccinated uninfected individuals (505±82 U/ml) and those with vaccine breakthrough infections (920±160 U/ml). Those with a third boosted vaccine dose had 4x higher IgG levels (2411±457 U/ml) compared to 2 dose vaccination. Vaccine breakthrough infection in the boosted cohort saw a decrease in IgG levels (568±157 U/ml) three days after infection with a recovery of increased IgG production to (1189±302 U/ml) by day 28. VP levels in the naturally infected unvaccinated cohort (4.4±0.6 μU/ml) and vaccine breakthrough infection cohort (3.8±0.4 μU/ml) were higher than the uninfected vaccinated cohort (2.3 ± 0.2 μU/ml) without altered osmotic regulation. Results show exposure to SARS-CoV-2 spike protein increases immune IgG stimulation in a dose dependent manner. Enhanced VP response related to SARS-CoV-2 infection is consistent with a putative VP role in virus infectivity independent of a physiological role of osmotic regulation in non-severe cases of COVID-19. The views expressed are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of Navy, Department of Defense, or the U.S. Government. This project was supported by the Joint Program Executive Office (JPEO-EB) W911QY-253 20-9-0004 (2020 OTA), and the Office of the Assistant Secretary of Defense for Health Affairs. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In the UK, over 1 million people live with diagnosed chronic obstructive pulmonary disease (COPD) however, it is estimated that this is only 1/3 of the total COPD population. Diagnosis is based on patient airflow obstruction, a late developing symptom, by which time a significant amount of lung damage has already occurred (1). Investigation into a range of biomarkers to aid earlier identification of COPD is therefore essential.Apical and basolateral samples collected from differentiated primary healthy and COPD cells at air liquid interface (ALI) were screened for 35 proteases, 32 protease inhibitors and 37 other inflammatory mediators using R&D Systems Proteome Profiler Protease array and Anti‐Protease array and BioRad Bio‐Plex Pro Human Inflammation Panel 1, 37‐Plex Assay respectively, with the aim of identifying potential biomarkers.Both apical and basolateral secretory profiles were altered in COPD samples compared to their healthy counterparts. The majority of apically secreted proteases were up‐regulated whereas, protease inhibitors were down‐regulated. Basolateral secretion of inflammatory mediators was found to be both up‐ and down‐regulated depending on which mediator was being measured.These initial results highlight interesting targets which will be further investigated in clinical samples to assess their potential as biomarkers to aid the earlier diagnosis of COPD.Support or Funding InformationBREATH (Border and REgions Airways Training Hub) is funded by the EU's INTERREG Va programme managed by the Special EU Programmes Body (SEUPB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.