RSS 1.0Allergy and Immunology
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Empty mast cell syndrome: fallacy or fact?Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as 'empty mast cell (MC) syndrome', is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4-6 weeks postanaphylaxis to avoid false-negative results.This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified.
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Antibody response to SARS-CoV-2 infection in humans: a systematic review.Background: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.
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The effect of smoking on Sjögren's disease development and severity: a comprehensive literature review.Unlike other autoimmune diseases, little is known about the environmental risk factors for Sjögren's disease (SjD). Smoking is an important risk factor for rheumatoid arthritis but the relationship between smoking and SjD is more complex to understand. Current smoking seems to be negatively linked to SjD, whereas there is mixed data on past smoking. Smoking also seems to impact SjD outcomes, influencing comorbidities like hypertension or associated immune-mediated diseases, and, less clearly, extraglandular involvement, particularly pulmonary disease. Minor salivary gland biopsy findings indicate a lower frequency of positivity associated with smoking, with a potential dose-response relationship. However, smoking's uncertain effect on dryness symptoms complicates interpretation of data with reverse causation remaining a possibility. This review underscores the complexity of the smoking-SjD connection, raising questions about causality and potential protective effects on either SjD's development and/or classification criteria. Understanding these nuances may help unravel SjD pathogenesis and inform future therapeutic strategies.
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Are ultrasound salivary parenchymal lesions more severe in primary Sjögren patients with a longer disease duration? A cross-sectional study.Objectives: Salivary gland ultrasound (SGUS) has an interest in primary Sjögren's disease (pSD) for diagnosis, but the evolution of parenchymal lesions over time is unknown. The objective of this study was to assess the severity of ultrasound abnormalities in relation to pSD duration from the time of buccal dryness onset. Methods: In this cross-sectional international multicentre study, patients with pSD according to the 2002 or 2016 ACR/EULAR classification criteria were included. Parenchymal abnormalities were classified according to the semiquantitative score as defined by OMERACT. Patients were separated into 4 groups (Group A: < 5 years, Group B: 5-9 years, Group C: 10-20 years, and Group D: > 20 years from the onset of buccal dryness). The association between disease duration groups and SGUS lesions was quantified in terms of odds ratios and 95% confidence intervals. Results: A total of 247 patients were consecutively included between May 2019 and February 2022. Eighty-nine percent of patients had a focus score ≥1/4 mm2, and 85% had positive anti-Ro/SSA. pSD duration was associated with a pathological OMERACT score (score 2 or 3): OR for 5-year duration: 1.23 [95% CI 1.04; 1.47], p= 0.0383). Considering each US item, the only statistical association with pSD duration was found regarding the presence of hyperechoic bands (25% or more): OR for five-year duration 1.18 [95% CI 1.03; 1.36], p= 0.038), independent of an older age. Conclusion: pSD duration was associated with the presence of hyperechoic bands, but not with hypoechoic areas, suggesting a progressive fibro-adipose evolution.
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Impact of the timing of immunotherapy administration on overall survival for resectable non-small cell lung cancer (iACORN study): A systematic review and meta-analysis of randomised trialsBackground: We sought to investigate the relative impact of the timing of the administration of immunotherapy on survival in patients with resectable lung cancer. Methods: We conducted a systematic review and meta-analysis of randomised controlled trials in this setting. We searched MEDLINE, EMBASE, LILACS and Cochrane Library databases from 1st January 1980 onwards. We excluded case reports; non-randomised studies; studies without an immunotherapy arm and if there was incomplete reporting on outcome data including conference abstracts. A standardised, pre-piloted form was used to extract data from the included studies for the assessment of study quality and for evidence synthesis. The primary outcome measure was overall survival which was assessed using random-effects meta-analyses (DerSimonian and Laird). The study was registered with PROSPERO (CRD42023407825). Findings: We screened 865 studies and assessed 58 full text articles after removing non-human, non-surgical studies. These studies collectively enrolled 4982 participants and 4425 were included in the respective analyses. Hazard ratios (HRs) for death by timing of administration of immunotherapy, i.e., Neoadjuvant (pre-operative), peri-operative and post-operative were 0.57 (95 % CI 0.302-1.08), 0.67 (95 % CI 0.39-1.13) and 0.94 (95 % CI 0.29-3.06) respectively. The timing of administration accounted for 100 % of the difference in true effect size (test of moderators (QM p = 0.127), residual I2 0 %, p = 0.561). OR for adverse events was higher in the neoadjuvant setting compared to the peri-operative setting; 1.49 (0.64-3.47) and 1.34 (1.08-1.66) respectively. Bias assessment found the majority of studies to be low risk with respect to random sequencing, incomplete outcomes, and selective reporting. Interpretation: In resectable non-small cell lung cancer, administration of adjuvant chemo-immunotherapy regimens in clinical trials did not lead to statistically significant survival benefits. Overall survival outcomes of neoadjuvant and peri-operative chemo-immunotherapy were comparable, but given the shorter duration and lower costs, neoadjuvant chemo-immunotherapy can be considered the current multimodality combination of choice.
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Outcomes of X-linked agammaglobulinaemia patientsBackground: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications. Objectives: To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies. Methods: Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed. Results: 99 patients with a median age of 29.02 years (IQR 12.83-37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04-8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT). Conclusions: Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy.
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Determinants of HBeAg loss during follow-up of a multiethnic pediatric cohortHepatitis B e antigen (HBeAg) loss is a key event in the natural history of chronic hepatitis B virus infection. The rate and determinants of HBeAg loss depend upon cohort characteristics at baseline. Few studies have examined the age-dependent rate, and none have examined the effect of patient sex and ethnicity on the age-dependant rate. The study of age-dependent rates requires the identification and long-term follow-up of a pediatric cohort. We have studied the age-dependent rate of HBeAg loss, and the rate of HBeAg loss measured from baseline, in a multi-ethnic cohort of 454 pediatric patients. During observation, HBeAg loss was observed in 121/303 (39.9%) HBeAg-positive patients. The rate of HBeAg loss was greater in the second versus the first and third decades of life. The age-related rate of HBeAg loss was clearly affected by patient sex and ethnicity, with earlier loss observed for males and for White versus both South Asian and Chinese ethnicities. When measured from baseline, Chinese patients had a slower rate of HBeAg loss in comparison with White patients. In multivariate analysis of HBeAg loss during prolonged follow-up, male sex, older age, and White ethnicity were associated with HBeAg loss, but antiviral treatment was not.
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A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel diseasePrecision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.
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Reverse-transcription loop-mediated isothermal amplification has high accuracy for detecting severe acute respiratory syndrome coronavirus 2 in saliva and nasopharyngeal/oropharyngeal swabs from asymptomatic and symptomatic IndividualsPrevious studies have described reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal/oropharyngeal swab and saliva samples. This multisite clinical evaluation describes the validation of an improved sample preparation method for extraction-free RT-LAMP and reports clinical performance of four RT-LAMP assay formats for SARS-CoV-2 detection. Direct RT-LAMP was performed on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva samples from asymptomatic and symptomatic individuals across health care and community settings. For direct RT-LAMP, overall diagnostic sensitivity (DSe) was 70.35% (95% CI, 63.48%-76.60%) on swabs and 84.62% (95% CI, 79.50%-88.88%) on saliva, with diagnostic specificity of 100% (95% CI, 98.98%-100.00%) on swabs and 100% (95% CI, 99.72%-100.00%) on saliva, compared with quantitative RT-PCR (RT-qPCR); analyzing samples with RT-qPCR ORF1ab CT values of ≤25 and ≤33, DSe values were 100% (95% CI, 96.34%-100%) and 77.78% (95% CI, 70.99%-83.62%) for swabs, and 99.01% (95% CI, 94.61%-99.97%) and 87.61% (95% CI, 82.69%-91.54%) for saliva, respectively. For RNA RT-LAMP, overall DSe and diagnostic specificity were 96.06% (95% CI, 92.88%-98.12%) and 99.99% (95% CI, 99.95%-100%) for swabs, and 80.65% (95% CI, 73.54%-86.54%) and 99.99% (95% CI, 99.95%-100%) for saliva, respectively. These findings demonstrate that RT-LAMP is applicable to a variety of use cases, including frequent, interval-based direct RT-LAMP of saliva from asymptomatic individuals who may otherwise be missed using symptomatic testing alone.
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Research priorities and strategies to improve asthma and allergy care in IndiaNo abstract available
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An appraisal of allergic disorders in India and an urgent call for action.India is the second most populous country in the world with a population of nearly 1.3 billion, comprising 20% of the global population. There are an estimated 37.5 million cases of asthma in India, and recent studies have reported a rise in prevalence of allergic rhinitis and asthma. Overall, 40-50% of paediatric asthma cases in India are uncontrolled or severe. Treatment of allergic rhinitis and asthma is sub-optimal in a significant proportion of cases due to multiple factors relating to unaffordability to buy medications, low national gross domestic product, religious beliefs, myths and stigma regarding chronic ailment, illiteracy, lack of allergy specialists, and lack of access to allergen-specific immunotherapy for allergic rhinitis and biologics for severe asthma. High quality allergen extracts for skin tests and adrenaline auto-injectors are currently not available in India. Higher postgraduate specialist training programmes in Allergy and Immunology are also not available. Another major challenge for the vast majority of the Indian population is an unacceptably high level of exposure to particulate matter (PM)2.5 generated from traffic pollution and use of fossil fuel and biomass fuel and burning of incense sticks and mosquito coils. This review provides an overview of the burden of allergic disorders in India. It appraises current evidence and justifies an urgent need for a strategic multipronged approach to enhance quality of care for allergic disorders. This may include creating an infrastructure for education and training of healthcare professionals and patients and involving regulatory authorities for making essential treatments accessible at subsidised prices. It calls for research into better phenotypic characterisation of allergic disorders, as evidence generated from high income western countries are not directly applicable to India, due to important confounders such as ethnicity, air pollution, high rates of parasitic infestation, and other infections.
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Investigating pulmonary and non-infectious complications in common variable immunodeficiency disorders: a UK national multi-centre studyBackground: Common Variable Immunodeficiency Disorders (CVID) encompass a spectrum of immunodeficiency characterised by recurrent infections and diverse non-infectious complications (NICs). This study aimed to describe the clinical features and variation in NICs in CVID with and without interstitial lung disease (ILD) from a large UK national registry population. Methods: Retrospective, cross-sectional data from a UK multicentre database (previously known as UKPIN), categorising patients into those with CVID-ILD and those with NICs related to CVID but without pulmonary involvement (CVID-EP; EP= extra-pulmonary involvement only). Results: 129 patients were included. Chronic lung diseases, especially CVID-ILD, are prominent complications in complex CVID, occurring in 62% of the cohort. Bronchiectasis was common (64% of the cohort) and associated with greater pulmonary function impairment in patients with CVID-ILD compared to those without bronchiectasis. Lymphadenopathy and the absence of gastrointestinal diseases were significant predictors of ILD in complex CVID. Although the presence of liver disease did not differ significantly between the groups, nearly half of the CVID-ILD patients were found to have liver disease. Patients with CVID-ILD were more likely to receive immunosuppressive treatments such as rituximab and mycophenolate mofetil than the CVID-EP group, indicating greater need for treatment and risk of complications. Conclusion: This study highlights the significant burden of CVID-ILD within the CVID population with NICs only. The lungs emerged as the most frequently affected organ, with ILD and bronchiectasis both highly prevalent. These findings emphasise the necessity of a comprehensive and multidisciplinary approach in managing CVID patients, considering their susceptibility to various comorbidities and complications.
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Comparison of short- and long-term humoral immune responses to pneumococcal polysaccharide and glycoconjugate vaccines in an HIV-infected populationBackground: Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort. Methods: We studied a subgroup of 152 of 839 participants from the AIR (Assessment of Immune Responses to Routine Immunisations in HIV-infected Adults, ISRCTN95588307) study that had received pneumococcal vaccinations and had blood samples collected pre- and post-vaccination, as well as at least annually for four subsequent calendar years. Patients received either Pneumovax-23 (PPV, N = 89) or Prevenar-13 (PCV, N = 63) as their primary vaccine, with immunity assessed by measuring IgG antibody concentrations for 12 pneumococcal polysaccharide serotypes (PnPS). The primary outcome was achieving IgG antibody concentrations above the recommended World Health Organisation (WHO) threshold of 0.35 µg/mL for at least 8/12 of the PnPS assessed (WHO≥8/12PnPS). Patients who did not achieve WHO≥8/12PnPS after the primary vaccination were offered further vaccination with PCV; booster vaccinations with PCV were additionally offered to those where antibody levels subsequently fell below the WHO≥8/12PnPS threshold. Results: Patients receiving PCV as their primary pneumococcal vaccine were significantly more likely to achieve WHO≥8/12PnPS after a single vaccine dose than those receiving PPV (54% vs. 33%, p = 0.012). This difference persisted following booster vaccination with PCV, with cumulative rates of WHO≥8/12PnPS in those receiving PCV vs. PPV as the primary vaccine of 88% vs. 67% and 100% vs. 85% after receiving up to one and two booster vaccinations, respectively. Where WHO≥8/12PnPS was achieved, this persisted significantly longer in those receiving PCV as their primary vaccine compared to PPV (median: 23.5 vs. 11.1 months; p = 0.010). Conclusions: Immunisation with PCV resulted in quantitatively greater antibody responses than immunisation with PPV in a cohort of HIV-infected UK adults. Individuals receiving PCV as their primary vaccine required fewer total pneumococcal vaccine doses to achieve WHO≥8/12PnPS and experienced greater duration of time above this threshold than those with PPV as the primary vaccine. However, the median longevity of both vaccine responses was relatively short, which supports the use of ongoing booster doses using high-valency glycoconjugate vaccines to sustain WHO≥8/12PnPS threshold antibody levels.
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Impact of senescent cell-derived extracellular vesicles on innate immune cell functionExtracellular vesicles (EVs) are components of the senescence-associated secretory phenotype (SASP) that influence cellular functions via their cargo. Here, the interaction between EVs derived from senescent (SEVs) and non-senescent (N-SEVs) fibroblasts and the immune system is investigated. Via endocytosis, SEVs are phagocytosed by monocytes, neutrophils, and B cells. Studies with the monocytic THP-1 cell line find that pretreatment with SEVs results in a 32% (p < 0.0001) and 66% (p < 0.0001) increase in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-α) production when compared to vehicle control or N-SEVs respectively. Interestingly, relative to vehicle control, THP-1 cells exposed to N-SEVs exhibit a 20% decrease in TNF-α secretion (p < 0.05). RNA sequencing reveals significant differences in gene expression in THP-1 cells treated with SEVs or N-SEVs, with vesicle-mediated transport and cell cycle regulation pathways featuring predominantly with N-SEV treatment, while pathways relating to SLITS/ROBO signaling, cell metabolism, and cell cycle regulation are enriched in THP-1 cells treated with SEVs. Proteomic analysis also reveals significant differences between SEV and N-SEV cargo. These results demonstrate that phagocytes and B cells uptake SEVs and drive monocytes toward a more proinflammatory phenotype upon LPS stimulation. SEVs may therefore contribute to the more proinflammatory immune response seen with aging.
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Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patientsBackground: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. Methods: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. Results: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). Conclusions: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.
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Understanding the role of host metabolites in the induction of immune senescence : future strategies for keeping the ageing population healthyAdvancing age is accompanied by significant remodelling of the immune system, termed immune senescence, and increased systemic inflammation, termed inflammageing, both of which contribute towards an increased risk of developing chronic diseases in old age. Age-associated alterations in metabolic homeostasis have been linked with changes in a range of physiological functions, but their effects on immune senescence remains poorly understood. In this article, we review the recent literature to formulate hypotheses as to how an age-associated dysfunctional metabolism, driven by an accumulation of key host metabolites (saturated fatty acids, cholesterol, ceramides and lactate) and loss of other metabolites (glutamine, tryptophan and short-chain fatty acids), might play a role in driving immune senescence and inflammageing, ultimately leading to diseases of old age. We also highlight the potential use of metabolic immunotherapeutic strategies targeting these processes in counteracting immune senescence and restoring immune homeostasis in older adults. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.
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Symptoms, complications and management of long COVID: a review.Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.
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Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugsTuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.