Cardiovascular medication adherence testing in patients living with HIV: A single-centre observational study.

INTRODUCTION: People with HIV (PWH) are at an increased risk of developing cardiovascular disease (CVD) compared to HIV-negative individuals. We sought to evaluate the adherence to medications for CVD in PWH and identify factors associated with non-adherence to these medications. METHODS: We conducted a cross-sectional study at the University Hospitals of Leicester NHS Trust between 16 April 2019 and 8 November 2022. We recruited consecutive PWH, who were attending a routine follow-up outpatient appointment and were prescribed at least one medication for CVD. In addition, we included urinary adherence results of patients with samples collected as part of routine clinical care. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess if their prescribed medications (antihypertensives, diuretics, beta-blockers, lipid-lowering agents, antiplatelets, anticoagulants, antidiabetic medications) were present in the participant's urine sample. Multivariable models were used to identify demographic or clinical features that were associated with non-adherence. RESULTS: A total of 162 PWH were included in the analysis. Median age was 55 [interquartile range (IQR): 50-61] years, 63% were male, average time living with HIV was 15 years (IQR: 11-19) and the majority (98%) had an undetectable HIV viral load. In approximately one-third of patients (59/162), at least one prescribed medication of interest was not detected in urine. Non-adherence to lipid-lowering agents was common (35/88, 40%). On multivariable logistic regression, the number of prescribed cardiovascular medications, was associated with medication non-adherence [medication non-adherence, per one medication increase: adjusted odds ratio (95% confidence interval) = 1.78 (1.34-2.36); p < 0.001]. CONCLUSION: We found sub-optimal adherence to medications for CVD in PWH. In order to maximize the clinical benefit of statin therapy in PWH, factors requiring consideration include: improved medication adherence, awareness of polypharmacy, educational interventions and quantitative assessment of sub-optimal adherence through chemical adherence testing.

Association between ethnicity and migration status with the prevalence of single and multiple long-term conditions in UK healthcare workers.

BACKGROUND: Healthcare workers' (HCW) well-being has a direct effect on patient care. However, little is known about the prevalence and patterns of long-term medical conditions in HCWs, especially those from ethnic minorities. This study evaluated the burden of multiple long-term conditions (MLTCs), i.e. the presence of two or more single long-term conditions (LTCs), among HCWs in the United Kingdom (UK) and variation by ethnicity and migration status. METHODS: We used baseline data from the UK-REACH cohort study collected December 2020-March 2021. We used multivariable logistic regression, adjusting for demographic, occupational and lifestyle factors to examine the relationship between self-reported LTCs/MLTCs and ethnicity, migration status and time since migration to the UK. RESULTS: Of 12,100 included HCWs, with a median age of 45 years (IQR: 34-54), 27% were overseas-born, and 30% were from non-White ethnic groups (19% Asian, 4% Black, 4% Mixed, 2% Other). The most common self-reported LTCs were anxiety (14.9%), asthma (12.2%), depression (10.7%), hypertension (8.7%) and diabetes (4.0%). Mental health conditions were more prevalent among UK-born than overseas-born HCWs for all ethnic groups (adjusted odds ratio (aOR) using White UK-born as the reference group each time: White overseas-born 0.77, 95%CI 0.66-0.95 for anxiety). Diabetes and hypertension were more common among Asian (e.g. Asian overseas, diabetes aOR 2.97, 95%CI 2.30-3.83) and Black (e.g. Black UK-born, hypertension aOR 1.77, 95%CI 1.05-2.99) groups than White UK-born. After adjustment for age, sex and deprivation, the odds of reporting MLTCs were lower in most ethnic minority groups and lowest for those born overseas, compared to White UK-born (e.g. White overseas-born, aOR 0.68, 95%CI 0.55-0.83; Asian overseas-born aOR 0.75, 95%CI 0.62-0.90; Black overseas-born aOR 0.52, 95%CI 0.36-0.74). The odds of MLTCs in overseas-born HCWs were equivalent to the UK-born population in those who had settled in the UK for ≥ 20 years (aOR 1.14, 95%CI 0.94-1.37). CONCLUSIONS: Among UK HCWs, the prevalence of common LTCs and odds of reporting MLTCs varied by ethnicity and migrant status. The lower odds of MLTCs in migrant HCWs reverted to the odds of MLTCs in UK-born HCWs over time. Further research on this population should include longitudinal studies with linkage to healthcare records. Interventions should be co-developed with HCWs from different ethnic and migrant groups focussed upon patterns of conditions prevalent in specific HCW subgroups to reduce the overall burden of LTCs/MLTCs.

Transmission of monkeypox/mpox virus: A narrative review of environmental, viral, host, and population factors in relation to the 2022 international outbreak.

Monkeypox virus (MPXV) has spread globally. Emerging studies have now provided evidence regarding MPXV transmission, that can inform rational evidence-based policies and reduce misinformation on this topic. We aimed to review the evidence on transmission of the virus. Real-world studies have isolated viable viruses from high-touch surfaces for as long as 15 days. Strong evidence suggests that the current circulating monkeypox (mpox) has evolved from previous outbreaks outside of Africa, but it is yet unknown whether these mutations may lead to an inherently increased infectivity of the virus. Strong evidence also suggests that the main route of current MPXV transmission is sexual; through either close contact or directly, with detection of culturable virus in saliva, nasopharynx, and sperm for prolonged periods and the presence of rashes mainly in genital areas. The milder clinical presentations and the potential presence of presymptomatic transmission in the current circulating variant compared to previous clades, as well as the dominance of spread amongst men who have sex with men (MSMs) suggests that mpox has a developed distinct clinical phenotype that has increased its transmissibility. Increased public awareness of MPXV transmission modalities may lead to earlier detection of the spillover of new cases into other groups.

High non-adherence rates to secondary prevention by chemical adherence testing in patients with TIA.

INTRODUCTION: Transient ischaemic attack (TIA) clinics are important for secondary prevention of fatal or disabling stroke. Non-adherence to prescribed medications is an important reason for treatment failure but difficult to diagnose. This study ascertained the utility of a novel biochemical tool in the objective biochemical diagnosis of non-adherence. METHODS: One-hundred consecutive urine samples collected from patients attending the TIA clinic, at a tertiary centre, were analysed for presence or absence of prescribed cardiovascular medications using liquid chromatography-mass spectrometry (LC-MS/MS). Patients were classified as adherent or non-adherent, respectively. Demographic and clinical characteristics were compared between the two cohorts. Univariate regression analyses were performed for individual variables and model fitting was undertaken for significant variables. RESULTS: The mean duration of follow-up from the index event was 31 days [standard deviation (SD): 18.9]. The overall rate of non-adherence for at least one medication was 24%. In univariate analysis, the number of comorbidities [3.4 (SD: 1.9) vs. 2.5 (1.9), P = 0.032] and total number of all prescribed medications [6.0 (3.3) vs 4.4 (2.1), P = 0.032] were higher in the non-adherent group. On multivariate analysis, the total number of medications prescribed correlated with increased non-adherence (odds ratio: 1.27, 95% Confidence Intervals: 1.1-1.5, P = 0.01). CONCLUSIONS: LC-MS/MS is a clinically useful tool for the diagnosis of non-adherence. Nearly a quarter of TIA patients were non-adherent to their cardiovascular medications Addressing non-adherence early may reduce the risk of future disabling cardiovascular events.

The need for improved discharge criteria for hospitalised patients with COVID-19-implications for patients in long-term care facilities.

In the COVID-19 pandemic, patients who are older and residents of long-term care facilities (LTCF) are at greatest risk of worse clinical outcomes. We reviewed discharge criteria for hospitalised COVID-19 patients from 10 countries with the highest incidence of COVID-19 cases as of 26 July 2020. Five countries (Brazil, Mexico, Peru, Chile and Iran) had no discharge criteria; the remaining five (USA, India, Russia, South Africa and the UK) had discharge guidelines with large inter-country variability. India and Russia recommend discharge for a clinically recovered patient with two negative reverse transcription polymerase chain reaction (RT-PCR) tests 24 h apart; the USA offers either a symptom based strategy-clinical recovery and 10 days after symptom onset, or the same test-based strategy. The UK suggests that patients can be discharged when patients have clinically recovered; South Africa recommends discharge 14 days after symptom onset if clinically stable. We recommend a unified, simpler discharge criteria, based on current studies which suggest that most SARS-CoV-2 loses its infectivity by 10 days post-symptom onset. In asymptomatic cases, this can be taken as 10 days after the first positive PCR result. Additional days of isolation beyond this should be left to the discretion of individual clinician. This represents a practical compromise between unnecessarily prolonged admissions and returning highly infectious patients back to their care facilities, and is of particular importance in older patients discharged to LTCFs, residents of which may be at greatest risk of transmission and worse clinical outcomes.

Squamous cell carcinoma arising from a vulval epidermal cyst.

Malignant transformation of epidermal cyst is rare, with most cases arising in the head and neck. Here, we report a case of squamous cell carcinoma arising from a longstanding epidermal cyst in the right vulva of a 65-year-old woman. The patient presented with a sudden increase in size of the cyst over 6 weeks to the size of a golf ball. Excisional biopsy and histology indicated moderately differentiated squamous cell carcinoma within an epidermal cyst (FIGO stage IB). Strong p16 immunopositivity was also demonstrated and the potential significance of this is discussed. Limited right hemivulvectomy and right groin node dissection were performed.

Compatibility of transvenous implantable cardioverter defibrillator and vagus nerve stimulation device: a case report.

Background: Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression. While VNS co-existence with cardiac pacemakers is considered safe, its interaction with implantable cardioverter defibrillators (ICDs) remains poorly understood. The concern revolves around the potential for VNS stimulation to interfere with ICD function, potentially resulting in inappropriate therapy or changes in cardiac pacing. Case summary: We present the case of a 50-year-old woman with drug-resistant epilepsy who underwent VNS device implantation and subsequent transvenous ICD placement for primary prevention post-myocardial infarction. These devices were thoughtfully situated contralaterally, with a minimum 10 cm separation. Comprehensive testing and follow-up demonstrated no interactions during device programming or serial assessments. Simultaneous interrogation of both devices with their respective telemetry wands caused chaotic artefacts in all channels on the ICD, likely due to electromagnetic interference. Importantly, this interference did not affect ICD sensing. Discussion: The co-existence of VNS and ICD in a patient is an emerging scenario with limited previous reports, yet our findings align with prior cases involving VNS and pacemakers. Emphasizing the need for optimal device separation and meticulous evaluation, particularly at maximum VNS output and ICD sensitivity settings, ensures their safe and feasible co-existence. As the use of VNS alongside cardiac implantable electronic devices becomes more common, a diligent evaluation for potential interactions is imperative. Our case highlights the successful co-existence of VNS and ICD, underscoring the importance of careful monitoring and evaluation to guarantee the safe utilization of these two devices.

Frailty in acute coronary syndromes. A systematic review and narrative synthesis of frailty assessment tools and interventions from randomised controlled trials.

AIM: We aimed to review all randomised controlled trial (RCT) data to explore optimal identification and treatment strategies of frail patients with Acute Coronary Syndromes (ACS). METHODS: The protocol was preregistered (PROSPERO - CRD42021250235). We performed a systematic review including RCT's that 1; used at least one frailty assessment tool to assess frailty and its impact on outcomes in patients diagnosed with ACS and 2; used at least one intervention where change in frailty was measured in patients diagnosed with ACS. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched on the 1st April 2021 and updated on 4th July 2023. Owing to low search output results are presented as a narrative synthesis of available evidence. RESULTS: A single RCT used a frailty assessment tool. A single RCT specifically targeted frailty with their intervention. This precluded further quantitative analysis. There was indication of selection bias against frail participants, and a signal of value for physical activity measurement in frail ACS patients. There was a high level of uncertainty and low level of robustness of this evidence. CONCLUSIONS: Data from RCT's alone is inadequate in answering the reviews question. Future RCT's need to address ways to incorporate frail participants, whilst mitigating selection biases. Physical performance aspects of the frailty syndrome appear to be high yield modifiable targets that improve outcomes. Intervention trials should consider using change in frailty status as an outcome measure. Any trials that include frail participants should present data specifically attributable to this group.

Implementation of facemask sampling for the detection of infectious individuals with SARS-CoV-2 in high stakes clinical examinations - a feasibility study.

Introduction: SARS-CoV-2 may transmit across vaccinated cohorts during practical clinical examinations. We sought to assess the feasibility of facemask sampling (FMS) to identify individuals emitting SARS-CoV-2 during a mock PACES exam. Methods: In May 2022 we recruited participants from a mock PACES examination in Leicester, UK. Following a negative lateral flow test assay, all participants wore modified facemasks able to capture exhaled virus during the assessment (FMS). A concomitant upper respiratory tract sample (URTS) was provided prior to FMS. Exposed facemasks were processed by removal and dissolution of sampling matrices fixed within the mask and cycle thresholds values quantified by RT-qPCR. Participants were asked to grade statements regarding the comfort, effort, ethics and communication when providing FMS; laboratory technicians were asked to grade key statements surrounding suitability of samples for processing. Results: 34 participants provided concomitant URTS and FMS during the examination. One participant was positive for SARS-CoV-2, with a cycle threshold value of 22.5 on URTS, but negative (no viral RNA detected) on FMS; no transmission to others was identified from this individual. Participants responded positively to statements regarding FMS describing all four domains; however, 69% of participants felt that a positive result from FMS alone was insufficient for diagnosis and that further tests were required. All but one FMS sample was suitable for processing. Discussion: FMS during PACES exams are acceptable among participants and samples provided are suitable for processing. Our results demonstrate feasibility of FMS within practical examination settings and support the further assessment of FMS as a scalable tool that can be compared with URTS to identify those who are infectious.

Changes in the investigation and management of suspected myocardial infarction and injury during COVID-19: a multi-centre study using routinely collected healthcare data.

Objective: The COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown. Methods: Multicentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3). Results: During the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased (p < 0.001), with greater likelihood of troponin testing in both chest pain (p = 0.001) and dyspnoea (p < 0.001). There was a dramatic reduction in elective and emergency cardiac procedures (both p < 0.001), and greater overall mortality of patients (p < 0.001), compared to the pre-pandemic period. Positive COVID-19 and/or troponin test results were associated with increased mortality (p < 0.001), though the temporal risk profile differed. Conclusions: The first wave of the COVID-19 pandemic was associated with significant changes not just in presentation, but also the investigation, management, and outcomes of patients presenting with suspected myocardial injury or MI.

Biomarkers in heart failure: a focus on natriuretic peptides.

While progress has been made in the management of most aspects of cardiovascular disease, the incidence and prevalence of heart failure (HF) remains high. HF affects around a million people in the UK and has a worse prognosis than most cancers. Patients with HF are often elderly with complex comorbidities, making accurate assessment of HF challenging. A timely diagnosis and initiation of evidence-based treatments are key to prevent hospitalisation and improve outcomes in this population. Biomarkers have dramatically impacted the way patients with HF are evaluated and managed. The most studied biomarkers in HF are natriuretic peptides (NPs). Since their discovery in the 1980s, there has been an explosion of work in the field of NPs and they have become an important clinical tool used in everyday practice to guide diagnosis and prognostic assessment of patients with HF. In this article, we will review the physiology of NPs and study their biological effects. Then, we will discuss the role of NPs in the diagnosis, management and prognostication of patients with HF. We will also explore the role of NPs as a potential therapeutic agent.

Which frailty tool best predicts morbidity and mortality in ambulatory patients with heart failure? A prospective study.

BACKGROUND: Frailty is common in patients with heart failure (HF) and is associated with adverse outcome, but it is uncertain how frailty should best be measured. OBJECTIVES: To compare the prognostic value of commonly-used frailty tools in ambulatory patients with HF. METHODS AND RESULTS: We assessed, simultaneously, three screening tools [clinical frailty scale (CFS); Derby frailty index (DFI); acute frailty network (AFN) frailty criteria), three assessment tools (Fried criteria; Edmonton frailty score (EFS); deficit index (DI)) and three physical tests (handgrip strength, timed get-up-and-go test (TUGT), 5-metre walk test (5MWT)] in consecutive patients with HF attending a routine follow-up visit. 467 patients (67% male, median age = 76 years, median NT-proBNP = 1156 ng/L) were enrolled. During a median follow-up of 554 days, 82 (18%) patients died and 201 (43%) patients were either hospitalised or died. In models corrected for age, Charlson score, haemoglobin, renal function, sodium, NYHA, atrial fibrillation (AF), and body mass index, only log[NT-proBNP] and frailty were independently associated with all-cause death. A base model for predicting mortality at 1 year including NYHA, log[NT-proBNP], sodium and AF, had a C-statistic = 0.75. Amongst screening tools: CFS (C-statistic = 0.84); amongst assessment tools: DI (C-statistic = 0.83) and amongst physical test: 5MWT (C-statistic = 0.80), increased model performance most compared with base model (P <0.05 for all). CONCLUSION: Frailty is strongly associated with adverse outcomes in ambulatory patients with HF. When added to a base model for predicting mortality at 1 year including NYHA, NT-proBNP, sodium, and AF, CFS provides comparable prognostic information with assessment tools taking longer to perform.

Exhaled SARS-CoV-2 RNA viral load kinetics measured by facemask sampling associates with household transmission.

OBJECTIVES: No studies have examined longitudinal patterns of naturally exhaled SARS-CoV-2 RNA viral load (VL) during acute infection. We report this using facemask sampling (FMS) and assessed the relationship between emitted RNA VL and household transmission. METHODS: Between December 2020 and February 2021, we recruited participants within 24 hours of a positive RT-qPCR on upper respiratory tract sampling (URTS) (day 0). Participants gave FMS (for 1 hour) and URTS (self-taken) on seven occasions up to day 21. Samples were analysed by RT-qPCR (from sampling matrix strips within the mask) and symptom diaries were recorded. Household transmission was assessed through reporting of positive URTS RT-qPCR in household contacts. RESULTS: Analysis of 203 FMS and 190 URTS from 34 participants showed that RNA VL peaked within the first 5 days following sampling. Concomitant URTS, FMS RNA VL, and symptom scores, however, were poorly correlated, but a higher severity of reported symptoms was associated with FMS positivity up to day 5. Of 28 participants who had household contacts, 12 (43%) reported transmission. Frequency of household transmission was associated with the highest (peak) FMS RNA VL obtained (negative genome copies/strip: 0% household transmission; 1 to 1000 copies/strip: 20%; 1001 to 10 000 copies/strip: 57%; >10 000 copies/strip: 75%; p = 0.048; age adjusted OR of household transmission per log increase in copies/strip: 4.97; 95% CI, 1.20-20.55; p = 0.02) but not observed with peak URTS RNA VL. DISCUSSION: Exhaled RNA VL measured by FMS is highest in early infection, can be positive in symptomatic patients with concomitantly negative URTS, and is strongly associated with household transmission.

Ethnic inequalities in COVID-19 infection, hospitalisation, intensive care admission, and death: a global systematic review and meta-analysis of over 200 million study participants.

Background: COVID-19 has exacerbated existing ethnic inequalities in health. Little is known about whether inequalities in severe disease and deaths, observed globally among minoritised ethnic groups, relates to greater infection risk, poorer prognosis, or both. We analysed global data on COVID-19 clinical outcomes examining inequalities between people from minoritised ethnic groups compared to the ethnic majority group. Methods: Databases (MEDLINE, EMBASE, EMCARE, CINAHL, Cochrane Library) were searched from 1st December 2019 to 3rd October 2022, for studies reporting original clinical data for COVID-19 outcomes disaggregated by ethnicity: infection, hospitalisation, intensive care unit (ICU) admission, and mortality. We assessed inequalities in incidence and prognosis using random-effects meta-analyses, with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) use to assess certainty of findings. Meta-regressions explored the impact of region and time-frame (vaccine roll-out) on heterogeneity. PROSPERO: CRD42021284981. Findings: 77 studies comprising over 200,000,000 participants were included. Compared with White majority populations, we observed an increased risk of testing positive for infection for people from Black (adjusted Risk Ratio [aRR]:1.78, 95% CI:1.59-1.99, I2 = 99.1), South Asian (aRR:3.00, 95% CI:1.59-5.66, I2 = 99.1), Mixed (aRR:1.64, 95% CI:1.02-1.67, I2 = 93.2) and Other ethnic groups (aRR:1.36, 95% CI:1.01-1.82, I2 = 85.6). Black, Hispanic, and South Asian people were more likely to be seropositive. Among population-based studies, Black and Hispanic ethnic groups and Indigenous peoples had an increased risk of hospitalisation; Black, Hispanic, South Asian, East Asian and Mixed ethnic groups and Indigenous peoples had an increased risk of ICU admission. Mortality risk was increased for Hispanic, Mixed, and Indigenous groups. Smaller differences were seen for prognosis following infection. Following hospitalisation, South Asian, East Asian, Black and Mixed ethnic groups had an increased risk of ICU admission, and mortality risk was greater in Mixed ethnic groups. Certainty of evidence ranged from very low to moderate. Interpretation: Our study suggests that systematic ethnic inequalities in COVID-19 health outcomes exist, with large differences in exposure risk and some differences in prognosis following hospitalisation. Response and recovery interventions must focus on tackling drivers of ethnic inequalities which increase exposure risk and vulnerabilities to severe disease, including structural racism and racial discrimination. Funding: ESRC:ES/W000849/1.

Pathways to ethnic inequalities in COVID-19 health outcomes in the United Kingdom: A systematic map.

BACKGROUND: Marked ethnic inequalities in COVID-19 infection and its consequences have been documented. The aim of this paper is to identify the range and nature of evidence on potential pathways which lead to ethnic inequalities in COVID-19 related health outcomes in the United Kingdom (UK). METHODS: We searched six bibliographic and five grey literature databases from 1st December 2019 to 23rd February 2022 for research on pathways to ethnic inequalities in COVID-19 health outcomes in the UK. Meta-data were extracted and coded, using a framework informed by a logic model. Open Science Framework Registration: DOI 10.17605/OSF.IO/HZRB7. RESULTS: The search returned 10,728 records after excluding duplicates, with 123 included (83% peer-reviewed). Mortality was the most common outcome investigated (N = 79), followed by infection (N = 52). The majority of studies were quantitative (N = 93, 75%), with four qualitative studies (3%), seven academic narrative reviews (6%), nine third sector reports (7%) and five government reports (4%), and four systematic reviews or meta-analyses (3%). There were 78 studies which examined comorbidities as a pathway to mortality, infection, and severe disease. Socioeconomic inequalities (N = 67) were also commonly investigated, with considerable research into neighbourhood infrastructure (N = 38) and occupational risk (N = 28). Few studies examined barriers to healthcare (N = 6) and consequences of infection control measures (N = 10). Only 11% of eligible studies theorised racism to be a driver of inequalities and 10% (typically government/third sector reports and qualitative studies) explored this as a pathway. CONCLUSION: This systematic map identified knowledge clusters that may be amenable to subsequent systematic reviews, and critical gaps in the evidence-base requiring additional primary research. Most studies do not incorporate or conceptualise racism as the fundamental cause of ethnic inequalities and therefore the contribution to literature and policy is limited.

Overstimulation of the ergoreflex-A possible mechanism to explain symptoms in long COVID.

Long COVID refers to a multitude of symptoms that persist long after SARS-CoV-2 infection. Fatigue and breathlessness are the most common symptoms of long COVID across a range of studies. They are also cardinal symptoms of chronic heart failure (CHF). In this review, we propose that fatigue and breathlessness in patients with long COVID may be explained by skeletal muscle abnormalities, in a manner similar to patients with CHF. The ergoreflex is a cardiorespiratory reflex activated by exercise, which couples ventilation and cardiovascular function to exercise intensity. At least part of the symptomatology of CHF is related to abnormal skeletal muscle and an enhanced ergoreflex, resulting in heightened sympathetic, vasoconstrictor and ventilator drives. Similarly, SARS-CoV-2 infection results in a hyperinflammatory and hypercatabolic state. This leads to reduction in skeletal muscle mass and altered function. We postulate that the ergoreflex is chronically overstimulated, resulting in fatigue and breathlessness. Exercise training preserves muscle mass and function as well as reduces ergoreflex activation; therefore may have a role in improving symptoms associated with long COVID. Should the ergoreflex be proven to be an important pathophysiological mechanism of long COVID, tailored exercise interventions should be trialed with the aim of improving both symptoms and perhaps outcomes in patients with long COVID.