43 research outputs found
Coral reef ecosystem services in the Anthropocene
Coral reefs underpin a range of ecosystem goods and services that contribute to the wellâbeing of millions of people. However, tropical coral reefs in the Anthropocene are likely to be functionally different from reefs in the past. In this perspective piece, we ask, what does the Anthropocene mean for the provision of ecosystem services from coral reefs? First, we provide examples of the provisioning, regulating, cultural and supporting services underpinned by coral reef ecosystems. We conclude that coral reef ecosystem service research has lagged behind multidisciplinary advances in broader ecosystem services science, such as an explicit recognition that interactions between social and ecological systems underpin ecosystem services. Second, drawing on tools from functional ecology, we outline how these socialâecological relationships can be incorporated into a mechanistic understanding of service provision and how this might be used to anticipate future changes in coral reef ecosystem services. Finally, we explore the emergence of novel reef ecosystem services, for example from tropicalized coastlines, or through changing technological connections to coral reefs. Indeed, when services are conceived as coming from socialâecological system dynamics, novelty in services can emerge from elements of the interactions between people and the ecosystem. This synthesis of the coral reef ecosystem services literature suggests the field is poorly prepared to understand the changing service provision anticipated in the Anthropocene. A new research agenda is needed that better connects reef functional ecology to ecosystem service provision. This research agenda should embrace more holistic approaches to ecosystem service research, recognizing them as coâproduced by ecosystems and society. Importantly, the likelihood of novel ecosystem service configurations requires further conceptualization and empirical assessment. As with current ecosystem services, the loss or gain of services will not affect all people equally and must be understood in the context in which they occur. With the uncertainty surrounding the future of coral reefs in the Anthropocene, research exploring how the benefits to people change will be of great importance
Evolution of precipitates, in particular cruciform and cuboid particles, during simulated direct charging of thin slab cast vanadium microalloyed steels
A study has been undertaken of four vanadium based steels which have been processed by a simulated direct charging route using processing parameters typical of thin slab casting, where the cast product has a thickness of 50 to 80mm ( in this study 50 mm) and is fed directly to a furnace to equalise the microstructure prior to rolling. In the direct charging process, cooling rates are faster, equalisation times shorter and the amount of deformation introduced during rolling less than in conventional practice. Samples in this study were quenched after casting, after equalisation, after 4th rolling pass and after coiling, to follow the evolution of microstructure. The mechanical and toughness properties and the microstructural features might be expected to differ from equivalent steels, which have undergone conventional processing. The four low carbon steels (~0.06wt%) which were studied contained 0.1wt%V (V-N), 0.1wt%V and 0.010wt%Ti (V-Ti), 0.1wt%V and 0.03wt%Nb (V-Nb), and 0.1wt%V, 0.03wt%Nb and 0.007wt%Ti (V-Nb-Ti). Steels V-N and V-Ti contained around 0.02wt% N, while the other two contained about 0.01wt%N. The as-cast steels were heated at three equalising temperatures of 1050C, 1100C or 1200C and held for 30-60 minutes prior to rolling. Optical microscopy and analytical electron microscopy, including parallel electron energy loss spectroscopy (PEELS), were used to characterise the precipitates. In the as-cast condition, dendrites and plates were found. Cuboid particles were seen at this stage in Steel V-Ti, but they appeared only in the other steels after equalization. In addition, in the final product of all the steels, fine particles were seen, but it was only in the two titanium steels that cruciform precipitates were present. PEELS analysis showed that the dendrites, plates, cuboids, cruciforms and fine precipitates were essentially nitrides. The two Ti steels had better toughness than the other steels but inferior lower yield stress values. This was thought to be, in part, due to the formation of cruciform precipitates in austenite, thereby removing nitrogen and the microalloying elements which would have been expected to precipitate in ferrite as dispersion hardening particles
BAs and boride III-V alloys
Boron arsenide, the typically-ignored member of the III-V arsenide series
BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma
conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an
X_1c-like indirect band gap, and its bond charge is distributed almost equally
on the two atoms in the unit cell, exhibiting nearly perfect covalency. The
reasons for these are tracked down to the anomalously low atomic p orbital
energy in the boron and to the unusually strong s-s repulsion in BAs relative
to most other III-V compounds. We find unexpected valence band offsets of BAs
with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is
significantly higher than that of AlAs, despite the much smaller bond length of
BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects
result from the unusually strong mixing of the cation and anion states at the
VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and
composition-independent band gap bowing. This means that while addition of
small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of
boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the
conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing
enthalpies which are smaller than in GaN-GaAs alloys. The unique features of
boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for
publication in Phys. Rev. B. Scheduled to appear Oct. 15 200
Desenvolvimento de um roteiro conceitual para a gestĂŁo da biodiversidade e dos serviços ecossistĂȘmicos no Caribe mexicano
Coral reefs and mangroves support rich biodiversity and provide ecosystem services that range from food, recreational benefits and coastal protection services, among others. They are one of the most threatened ecosystems by urbanization processes. In this context, we developed a conceptual framework for the management of biodiversity and ecosystem services for these coastal environments. We based our workflow on two sections: âInformation baseâ and âGovernanceâ and use the Puerto Morelos Coastal region as a case study for coastal protection. Puerto Morelos is between two of the most touristic destinations of Mexico (Playa del Carmen and Cancun) that has experienced an increase of population in the past four decades resulting in an intensification of multiple threats to its ecosystems. We characterized the two ecosystems with a âManagement Unitsâ strategy. An expert-based ecosystem services matrix was also described in order to connect mangroves and coral reef ecosystems with the multiple beneficiaries. Then an ecosystem model (conceptual model and Global Biodiversity model) was developed. The conceptual model was useful in understanding the interplay processes between systems regarding the ecosystem service of âCoastal Protectionâ. The Global Biodiversity model evidenced the human-induced shifts in the biodiversity for mangrove and coral reefs ecosystems. Also, a projection for 2035 of âbestâ and âworstâ scenarios was applied using GLOBIO3. A DPSIR conceptual framework was used to analyze environmental problems regarding ecosystem services maintenance. Finally, we evaluated a set of policies associated with these ecosystems that favor coastal protection integrity. This framework facilitates the identification of the most relevant processes and controls about the provision of coastal protection service. It can also be useful to better target management actions and as a tool to identify future management needs to tackle the challenges preventing more effective conservation of coastal environments.Recifes de coral e manguezais possuem rica biodiversidade e fornecem serviços ecossistĂȘmicos, tais como, alimento, recreação, proteção costeira, entre outros. Esses ecossistemas encontram-se entre os mais ameaçados pelos processos de urbanização. Nesse contexto, desenvolvemos um roteiro conceitual para a gestĂŁo da biodiversidade e dos serviços ecossistĂȘmicos desses ambientes costeiros. Organizamos nossa sequĂȘncia de passos de trabalho em duas seçÔes: âBase de informaçÔesâ e âGovernançaâ e usamos a regiĂŁo costeira da cidade de Puerto Morelos (MĂ©xico) como um estudo de caso para analisar o serviço de proteção de costa. Puerto Morelos encontra-se entre dois dos destinos mais turĂsticos do MĂ©xico (Playa del Carmen e CancĂșn), e portanto sua população vem aumentando nas Ășltimas quatro dĂ©cadas, resultando na intensificação de mĂșltiplas ameaças para os ecossistemas. Primeiramente, caracterizamos os dois ecossistemas identificando-os como âUnidades de GestĂŁoâ, detalhando seus principais componentes e processos. AtravĂ©s de uma âMatriz de serviços ecossistĂȘmicosâ, construĂda com base na opiniĂŁo de especialistas, foram sistematizados os principais serviços ecossistĂȘmicos prestados pelos manguezais e recifes de corais aos mĂșltiplos beneficiĂĄrios. Em seguida, foi desenvolvida uma modelagem do sistema (e ecossistemas) atravĂ©s de sua representação na forma de um modelo conceitual e um modelo numĂ©rico de Biodiversidade Global. O modelo conceitual facilitou a compreensĂŁo dos processos de interação entre sistemas em relação ao serviço âProteção Costeiraâ. O modelo numĂ©rico evidenciou as mudanças induzidas pelo homem na biodiversidade dos ecossistemas de manguezal e recifes de coral. AlĂ©m disso, uma projeção dos cenĂĄrios âmelhorâ e âpiorâ foi desenvolvida para 2035 usando GLOBIO3. A Estrutura conceitual DPSIR foi aplicada para analisar problemas ambientais relacionados Ă manutenção dos serviços ecossistĂȘmicos. Finalmente, avaliamos um conjunto de polĂticas pĂșblicas associadas a esses ecossistemas e que favorecem a integridade da proteção costeira. Portanto, o roteiro facilitou a identificação dos principais processos e controles para a provisĂŁo de um serviço ecossistĂȘmico. AlĂ©m disso, pode ser Ăștil para direcionar melhor as açÔes de gerenciamento, bem como, uma ferramenta para identificar necessidades futuras de planejamento e gestĂŁo para enfrentar desafios que permitam uma conservação mais eficaz dos ambientes costeiros.Fil: SĂĄnchez Quinto, AndrĂ©s. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: Costa, Julliet Correa da. Universidade Federal de Santa Catarina; BrasilFil: Zamboni, Nadia Selene. Universidade Federal do Rio Grande do Norte; BrasilFil: Sanches, FĂĄbio H. C.. Universidade Federal de Sao Paulo; BrasilFil: Principe, Silas C.. Universidade de Sao Paulo; BrasilFil: Viotto, Evangelina del Valle. Provincia de Entre RĂos. Centro de Investigaciones CientĂficas y Transferencia de TecnologĂa a la ProducciĂłn. Universidad AutĂłnoma de Entre RĂos. Centro de Investigaciones CientĂficas y Transferencia de TecnologĂa a la ProducciĂłn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Santa Fe. Centro de Investigaciones CientĂficas y Transferencia de TecnologĂa a la ProducciĂłn; ArgentinaFil: Casagranda, Maria Elvira. Universidad Nacional de TucumĂĄn. Instituto de EcologĂa Regional. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - TucumĂĄn. Instituto de EcologĂa Regional; ArgentinaFil: Lima, Francisco A. da Veiga. Universidade Federal de Santa Catarina; BrasilFil: Possamai, Bianca. Universidade Federal Do Rio Grande.; BrasilFil: Faroni Perez, Larisse. Universidade Federal de Juiz de Fora; Brasi
A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial
Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48â0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78â2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation
Accelarated immune ageing is associated with COVID-19 disease severity
Background
The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.
Results
We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3â5 months post recovery who were classified as having had severe (nâ=â56; age 53.12â±â11.30 years), moderate (nâ=â32; age 52.28â±â11.43 years) or mild (nâ=â15; age 49.67â±â7.30 years) disease and compared with age and sex-matched healthy adults (nâ=â59; age 50.49â±â10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naĂŻve CD4 and CD8 T cells (pâ<â0.0001); increased frequency of EMRA CD4 (pâ<â0.003) and CD8 T cells (pâ<â0.001); a higher frequency (pâ<â0.0001) and absolute numbers (pâ<â0.001) of CD28âve CD57+ve senescent CD4 and CD8 T cells; higher frequency (pâ<â0.003) and absolute numbers (pâ<â0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (pâ<â0.0001); higher frequency of memory B cells (pâ<â0.001) and increased frequency (pâ<â0.0001) and numbers (pâ<â0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (pâ<â0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (
= 0.174, pâ=â0.043), with a major influence being disease severity (
= 0.188, pâ=â0.01).
Conclusions
Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease
Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study
Background:
Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea.
Methods:
CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2â7 months after hospital discharge and a later time point 10â14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107).
Findings:
2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4â6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5â8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (â19%; 95% CI â20 to â16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18â39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27â41% of this effect.
Interpretation:
Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition.
Funding:
UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council
Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study
Introduction:
The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.
Methods:
In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged â„18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.
Findings:
Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2â6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23â11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.
Interpretation:
After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.
Funding:
UK Research and Innovation and National Institute for Health Research
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
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 â„3âmonths 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 brainâgut 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