Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

The influence of gas and liquid flow rates on the transient bubble characteristics in a liquid cross-flow

The paper reports on an experimental study conducted to investigate the dynamics of gas bubbles when injected from an orifice that is subjected to a liquid cross-flow. The experiments were conducted over a range of gas and liquid flow rates and at various orientations of the liquid channel. An image processing algorithm was developed for the detection and characterization of the bubbles in both temporal and spatial coordinates. The transient behaviour of bubble dynamics at different channel orientations under different liquid and gas flow conditions are presented in the paper. Results show that the equivalent bubble diameter in the vertical plane decreased with increase in time as well as with increase in the gas-to-liquid velocity ratio. The channel inclination has no appreciable effect on the bubble diameter. The streamwise bubble velocity showed significant transient fluctuations, which diminished with an increase in the channel inclination angle. The fluctuations of the bubble vertical velocity were found to be unaffected by the channel inclination angle. The magnitudes of both streamwise and vertical velocities were influenced by the channel inclination, however, the trends were found to be opposite. Copyright \ua9 2011 by ASME.Peer reviewed: YesNRC publication: Ye

The effect of nozzle shape and configuration on bubble formation in a liquid cross flow

Gas injection into a liquid cross flow from a nozzle causes bubble formations which have potential applications in industry such as chemical plants, waste water treatment and bio- and nuclear-reactors. The purpose of this study is to experimentally investigate the effects of nozzle shape and configuration with respect to the liquid cross-flow direction, on the bubbly flow characteristics such as bubble formation, detached bubble size and frequency at different gas and liquid flow rates. The experiments were conducted in a Plexiglas two-dimensional rig using a high speed camera. High speed imaging and an image processing algorithm were used to track each individual bubble and to quantify the bubble growth as well as the detachment frequency and the bubble velocity. Back light shadowgraphy which utilizes a low intensity diffuse light source to illuminate the background was used to image bubbles. Nozzles were mounted in the test section which was designed such that the flow in this section has a two-dimensional profile. The results showed that the bubble size increases with an increase in GLR (gas to liquid flow rates ratio). Furthermore, the bubble formations and detached bubble size were strongly influenced by the nozzle shape and configuration. Copyright \ua9 2012 by ASME.Peer reviewed: YesNRC publication: Ye

Investigation of two-phase flow in an effervescent atomizer

Aerated-liquid atomization, also called "effervescent atomization", is a technique that has a wide range of applications such as gas turbine combustors, internal combustion engines, furnaces and burners, and pharmaceutical sprays. We report on an experimental study conducted to investigate the two-phase flow in an Effervescent atomizer. A novel aerator tube base was implemented and tested. It is observed that the novel configuration suppresses the separation bubble at the trailing edge and results in more uniform and smaller bubbles compared to the standard flat base aerator. It has been found that the more uniform and smaller bubbles are generated as the mixing chamber length is reduced. It is concluded that by using a conical base aerator and by reducing the mixing chamber length, the spray steadiness and the atomization process can be significantly improved.Peer reviewed: YesNRC publication: N