The physiologic benefits of optimizing cardiorespiratory fitness and physical activity - From the cell to systems level in a post-pandemic world.

Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA.

Using cardiorespiratory fitness assessment to identify pathophysiology in long COVID - Best practice approaches.

Cardio-respiratory fitness (CRF) is well-established in the clinical domains as an integrative measure of the body's physiological capability and capacity to transport and utilise oxygen during controlled bouts of physical exertion. Long COVID is associated with >200 different symptoms and is estimated to affect ∼150 million people worldwide. The most widely reported impact is reduced quality of life and functional status due to highly sensitive and cyclical symptoms that manifest and are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli, more commonly known as post-exertional symptom exacerbation (PESE) which prevents millions from engaging in routine daily activities. The use of cardiopulmonary exercise testing (CPET) is commonplace in the assessment of integrated physiology; CPET will undoubtedly play an integral role in furthering the pathophysiology and mechanistic knowledge that will inform bespoke Long COVID treatment and management strategies. An inherent risk of previous attempts to utilise CPET protocols in patients with chronic disease is that these are compounded by PESE and have induced a worsening of symptoms for patients that can last for days or weeks. To do this effectively and to meet the global need, the complex multi-system pathophysiology of Long COVID must be considered to ensure the design and implementation of research that is both safe for participants and capable of advancing mechanistic understanding.

Long COVID quality of life and healthcare experiences in the UK: a mixed method online survey.

PURPOSE: The complexity of long COVID and its diverse symptom profile contributes to unprecedented challenges for patients, clinicians, and healthcare services. The threat of long COVID remains ignored by Governments, the media and public health messaging, and patients' experiences must be heard through understanding of the lived experience. This study aimed to understand the lived experience of those living with long COVID. METHODS: An online web-based survey was designed using Patient and Public Involvement and Engagement (PPIE) to increase understanding of the lived experiences of long COVID, and was distributed through PPIE groups, social media, and word of mouth. The survey used closed and open questions relating to demographics, pre- and post-COVID-19 health quality of life, daily activities and long COVID experiences. RESULTS: Within our sample of 132 people living with long COVID, the findings highlight that individuals are being severely impacted by their symptoms and are unable to or limited in participating in their daily activities, reducing quality of life. Long COVID places strain on relationships, the ability to live life fully and is detrimental to mental health. Varying health care experiences are described by participants, with reports of medical gaslighting and inadequate support received. CONCLUSIONS: Long COVID has a severe impact on the ability to live life fully, and strains mental health. The appropriate mechanisms and support services are needed to support those living with long COVID and manage symptoms.

Forming a consensus opinion to inform long COVID support mechanisms and interventions: a modified Delphi approach.

Background: Current approaches to support patients living with post-COVID condition, also known as Long COVID, are highly disparate with limited success in managing or resolving a well-documented and long-standing symptom burden. With approximately 2.1 million people living with the condition in the UK alone and millions more worldwide, there is a desperate need to devise support strategies and interventions for patients. Methods: A three-round Delphi consensus methodology was distributed internationally using an online survey and was completed by healthcare professionals (including clinicians, physiotherapists, and general practitioners), people with long COVID, and long COVID academic researchers (round 1 n = 273, round 2 n = 186, round 3 n = 138). Across the three rounds, respondents were located predominantly in the United Kingdom (UK), with 17.3-15.2% (round 1, n = 47; round 2 n = 32, round 2 n = 21) of respondents located elsewhere (United States of America (USA), Austria, Malta, United Arab Emirates (UAE), Finland, Norway, Malta, Netherlands, Iceland, Canada, Tunisie, Brazil, Hungary, Greece, France, Austrailia, South Africa, Serbia, and India). Respondents were given ∼5 weeks to complete the survey following enrolment, with round one taking place from 02/15/2022 to 03/28/22, round two; 05/09/2022 to 06/26/2022, and round 3; 07/14/2022 to 08/09/2022. A 5-point Likert scale of agreement was used and the opportunity to include free text responses was provided in the first round. Findings: Fifty-five statements reached consensus (defined as >80% agree and strongly agree), across the domains of i) long COVID as a condition, ii) current support and care available for long COVID, iii) clinical assessments for long COVID, and iv) support mechanisms and rehabilitation interventions for long COVID, further sub-categorised by consideration, inclusion, and focus. Consensus reached proposes that long COVID requires specialised, comprehensive support mechanisms and that interventions should form a personalised care plan guided by the needs of the patients. Supportive approaches should focus on individual symptoms, including but not limited to fatigue, cognitive dysfunction, and dyspnoea, utilising pacing, fatigue management, and support returning to daily activities. The mental impact of living with long COVID, tolerance to physical activity, emotional distress and well-being, and research of pre-existing conditions with similar symptoms, such as myalgic encephalomyelitis, should also be considered when supporting people with long COVID. Interpretation: We provide an outline that achieved consensus with stakeholders that could be used to inform the design and implementation of bespoke long COVID support mechanisms. Funding: None.

Lived experience of patients with Long COVID: a qualitative study in the UK.

BACKGROUND: Long COVID is a rapidly evolving global health crisis requiring interdisciplinary support strategies that incorporate the lived experience of patients. Currently, there is a paucity of research documenting the day-to-day experiences of patients living with Long COVID. OBJECTIVE: To explore the lived experience of Long COVID patients. STUDY DESIGN: Longitudinal, observation study. SETTING: An inductive, data-driven, qualitative approach was used to evaluate hand-written diaries obtained from individuals who had been referred to a Derbyshire Long COVID clinic. PARTICIPANTS: 12 participants (11 females, age 49±10 years, 11 Caucasians) were recruited. Participants were included if they had a previous confirmed or suspected COVID-19 infection with ongoing recovery, >18 years old, understood the study requirements and provided informed consent. METHOD: Participants were directed to complete self-report diaries over 16 weeks. Responses were transcribed verbatim and analysed using thematic analysis. RESULTS: Three key themes were highlighted: (1) understanding who helps patients manage symptoms, (2) daily activities and the impact on quality of life and health status and (3) the effect of turbulent and episodic symptom profiles on personal identity and recovery. CONCLUSIONS: The novel challenges presented by Long COVID are complex with varying inter-related factors that are broadly impacting functional status and quality of life. Support mechanisms must incorporate the lived experiences and foster true collaborations between health professionals, patients and researchers to improve patient outcomes. TRIAL REGISTRATION NUMBER: NCT04649957.

A united approach to promoting healthy living behaviours and associated health outcomes: a global call for policymakers and decisionmakers.

Chronic disease pandemics have challenged societies and public health throughout history and remain ever-present. Despite increased knowledge, awareness and advancements in medicine, technology, and global initiatives the state of global health is declining. The coronavirus disease 2019 (COVID-19) pandemic has compounded the current perilous state of global health, and the long-term impact is yet to be realised. A coordinated global infrastructure could add substantial benefits to public health and yield prominent and consistent policy resulting in impactful change. To achieve global impact, research priorities that address multi-disciplinary social, environmental, and clinical must be supported by unified approaches that maximise public health. We present a call to action for established public health organisations and governments globally to consider the lessons from the COVID-19 pandemic and unite with true collaborative efforts to address current, longstanding, and growing challenges to public health.

The Impact of COVID-19 on the Social Determinants of Cardiovascular Health.

Cardiovascular disease is the leading noncommunicable disease and cause of premature mortality globally. Despite well established evidence of a cause-effect relationship between modifiable lifestyle behaviours and the onset of risk of chronic disease, preventive approaches to curtail increasing prevalence have been ineffective. This has undoubtedly been exacerbated by the response to COVID-19, which saw widespread national lockdowns implemented to reduce transmission and alleviate pressure on strained health care systems. A consequence of these approaches was a well documented negative impact on population health in the context of both physical and mental well-being. Although the true extent of the impact of the COVID-19 response on global health has yet to be fully realised or understood, it seems prudent to review effective preventative and management strategies that have yielded positive outcomes across the spectrum (ie, from individual to society). There is also a clear need to heed lessons learned from the COVID-19 experience in the power of collaboration and how this can be used in the design, development, and implementation of future approaches to address the longstanding burden of cardiovascular disease.

Cardiovascular disease prevention and management in the COVID-19 era and beyond: An international perspective.

Despite some indicators of a localized curtailing of cardiovascular disease (CVD) prevalence, CVD remains one of the largest contributors to global morbidity and mortality. While the magnitude and impact of the coronavirus disease 2019 (COVID-19) pandemic have yet to be realized in its entirety, an unquestionable impact on global health and well-being is already clear. At a time when the global state of CVD is perilous, we provide a continental overview of prevalence data and initiatives that have positively influenced CVD outcomes. What is clear is that despite attempts to address the global burden of CVD, there remains a lack of collective thinking and approaches. Moving forward, a coordinated global infrastructure that, if developed with appropriate and relevant key stakeholders, could provide significant and longstanding benefits to public health and yield prominent and consistent policy resulting in impactful change. To achieve global impact, research priorities that address multi-disciplinary social, environmental, and clinical perspectives must be underpinned by unified approaches that maximize public health.

The acute and chronic implications of the COVID-19 virus on the cardiovascular system in adults: A systematic review.

Despite coronavirus disease 2019 (COVID-19) primarily being identified as a respiratory illness, some patients who seemingly recovered from initial infection, developed chronic multi-system complications such as cardiovascular (CV), pulmonary and neurological issues leading to multiple organ injuries. However, to date, there is a dearth of understanding of the acute and chronic implications of a COVID-19 infection on the CV system in adults. A systematic review of the literature was conducted according to PRISMA guidelines and prospectively registered via Prospero (ID: CRD42022360444). The MEDLINE Ovid, Cochrane Library and PubMed databases were searched from inception to August 2022. The search strategy keywords and MeSH terms used included: 1) COVID; 2) coronavirus; 3) long COVID; 4) cardiovascular; and 5) cardiovascular disease. Reference lists of all relevant systematic reviews identified were searched for additional studies. A total of 11,332 records were retrieved from database searches, of which 310 records were duplicates. A further 9887 were eliminated following screening of titles and abstracts. After full-text screening of 1135 articles, 9 manuscripts were included for review. The evidence of CV implications post-COVID-19 infection is clear, and this must be addressed with appropriate management strategies that recognise the acute and chronic nature of cardiac injury in COVID-19 patients. Efficacious management strategies will be needed to address long standing issues and morbidity.

Cardiorespiratory fitness as a vital sign of CVD risk in the COVID-19 era.

The severe health consequences of the corona virus disease 2019 (COVID-19) pandemic have been exacerbated by the prevalence of cardiovascular disease (CVD) risk factors, such as physical inactivity, obesity, hypertension, and diabetes. Further, policy decisions during the pandemic augmented unhealthy lifestyle behaviors and health inequalities, likely increasing the global disease burden. Cardiorespiratory fitness (CRF) is a well-established biomarker associated with CVD risk. Emerging data demonstrate that high CRF offers some protection against severe outcomes from COVID-19 infection, highlighting the importance of CRF for population health and the potential for limiting the severity of future pandemics. CRF is best assessed by cardiopulmonary exercise testing (CPET), which will be an important tool for understanding the prolonged pathophysiology of COVID-19, the emergence of long-COVID, and the lasting effects of COVID-19 on CVD risk. Utilization of CRF and CPET within clinical settings should become commonplace because of lessons learned from the COVID-19 pandemic.

COVID-19 and elite sport: Cardiovascular implications and return-to-play.

Curtailing elite sports during the coronavirus disease 2019 (COVID-19) pandemic was necessary to prevent widespread viral transmission. Now that elite sport and international competitions have been largely restored, there is still a need to devise appropriate screening and management pathways for athletes with a history of, or current, COVID-19 infection. These approaches should support the decision-making process of coaches, sports medicine practitioners and the athlete about the suitability to return to training and competition activities. In the absence of longitudinal data sets from athlete populations, the incidence of developing prolonged and debilitating symptoms (i.e., Long COVID) that affects a return to training and competition remains a challenge to sports and exercise scientists, sports medicine practitioners and clinical groups. As the world attempts to adjust toward 'living with COVID-19' the very nature of elite and international sporting competition poses a risk to athlete welfare that must be screened for and managed with bespoke protocols that consider the cardiovascular implications for performance.

The need for exercise sciences and an integrated response to COVID-19: A position statement from the international HL-PIVOT network.

COVID-19 is one of the biggest health crises that the world has seen. Whilst measures to abate transmission and infection are ongoing, there continues to be growing numbers of patients requiring chronic support, which is already putting a strain on health care systems around the world and which may do so for years to come. A legacy of COVID-19 will be a long-term requirement to support patients with dedicated rehabilitation and support services. With many clinical settings characterized by a lack of funding and resources, the need to provide these additional services could overwhelm clinical capacity. This position statement from the Healthy Living for Pandemic Event Protection (HL-PIVOT) Network provides a collaborative blueprint focused on leading research and developing clinical guidelines, bringing together professionals with expertise in clinical services and the exercise sciences to develop the evidence base needed to improve outcomes for patients infected by COVID-19.

Supported progressive resistance exercise training to counter the adverse side effects of robot-assisted radical prostatectomy: a randomised controlled trial.

PURPOSE: To investigate the effects of a supported home-based progressive resistance exercise training (RET) programme on indices of cardiovascular health, muscular strength and health-related quality of life (HR-QoL) in prostate cancer (PCa) patients after treatment with robot-assisted radical prostatectomy (RARP). METHODS: This study was a single-site, two-arm randomised controlled trial, with 40 participants randomised to either the intervention or control group over a 10-month period. In addition to receiving usual care, the intervention group completed three weekly RET sessions using resistance bands for 6 months. Participants performed 3 sets of 12-15 repetitions for each exercise, targeting each major muscle group. The control group received usual care only. Brachial artery flow-mediated dilatation (FMD) was the primary outcome and assessed at baseline, 3 and 6 months. Secondary outcomes included body weight, body fat, aerobic fitness, strength and blood-borne biomarkers associated with cardiometabolic risk. RESULTS: There was no significant difference between the groups in FMD at 3 or 6 months. However, there were improvements in aerobic exercise capacity (P < 0.01) and upper- (P < 0.01) and lower-limb (P = 0.01) strength in favour of the RET group at 6 months, accompanied by greater weight loss (P = 0.04) and a reduction in body fat (P = 0.02). Improvements in HRQoL were evident in the RET group at 3 and 6 months via the PCa-specific component of the FACT-P questionnaire (both P < 0.01). Five adverse events and one serious adverse event were reported throughout the trial duration. CONCLUSION: This study demonstrates that home-based RET is an effective and safe mode of exercise that elicits beneficial effects on aerobic exercise capacity, muscular strength and HR-QoL in men who have undergone RARP. TRIAL REGISTRATION: ISRCTN10490647.

Effects of short-term, medium-term and long-term resistance exercise training on cardiometabolic health outcomes in adults: systematic review with meta-analysis.

OBJECTIVE: To examine the effects of short-term, medium-term and long-term resistance exercise training (RET) on measures of cardiometabolic health in adults. DESIGN: Intervention systematic review. DATA SOURCES: MEDLINE and Cochrane Library databases were searched from inception to February 2018. The search strategy included the following keywords: resistance exercise, strength training and randomised controlled trial. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials published in English comparing RET≥2 weeks in duration with a non-exercising control or usual care group. Participants were non-athletic and aged ≥18 years. RESULTS: A total of 173 trials were included. Medium-term and long-term RET reduced systolic blood pressure (-4.02 (95% CI -5.92 to -2.11) mm Hg, p<0.0001 and -5.08 (-10.04 to -0.13) mm Hg, p=0.04, respectively) and diastolic blood pressure (-1.73 (-2.88 to -0.57) mm Hg, p=0.003 and -4.93 (-8.58 to -1.28) mm Hg, p=0.008, respectively) versus control. Medium-term RET elicited reductions in fasted insulin and insulin resistance (-0.59 (-0.97 to -0.21) µU/mL, p=0.002 and -1.22 (-2.29 to -0.15) µU/mL, p=0.02, respectively). The effects were greater in those with elevated cardiometabolic risk or disease compared with younger healthy adults. The quality of evidence was low or very low for all outcomes. There was limited evidence of adverse events. CONCLUSIONS: RET may be effective for inducing improvements in cardio metabolic health outcomes in healthy adults and those with an adverse cardio metabolic risk profile. PROSPERO REGISTRATION NUMBER: CRD42016037946.

Cross-sectional study of patient-reported fatigue, physical activity and cardiovascular status in men after robotic-assisted radical prostatectomy.

PURPOSE: Patient-reported fatigue after robotic-assisted radical prostatectomy (RARP) has not been characterised to date. Fatigue after other prostate cancer (PCa) treatments is known to impact on patient-reported quality of life. The aim of this study was to characterise fatigue, physical activity levels and cardiovascular status post-RARP. METHODS: Between October 2016 and March 2017, men post-RARP or on androgen deprivation therapy (ADT) were invited into the study. Participants were asked to complete the Brief Fatigue Inventory (BFI) and Stage of Change and Scottish Physical Activity Questionnaires (SPAQ) over a 2-week period. Outcome measures were patient-reported fatigue, physical activity levels and the 10-year risk of cardiovascular disease (Q-Risk). Data were analysed in SPSS. RESULTS: 96/117 (82%) men approached consented to participate; of these, 62/96 (65%) returned complete questionnaire data (RARP n = 42, ADT n = 20). All men reported fatigue with 9/42 (21%) post-RARP reporting clinically significant fatigue. Physical activity did not correlate with fatigue. On average, both groups were overweight (BMI 27.0 ± 3.9 kg/m2 and 27.8 ± 12.3 kg/m2 for RARP and ADT, respectively) and the post-RARP group had an 18.1% ± 7.4% Q-Risk2 score. CONCLUSIONS: A proportion of men is at increased risk of cardiovascular disease within 10 years post-RARP and have substantial levels of fatigue; therefore, clinicians should consider including these factors when counselling patients about RARP. Additionally, men post-RARP did not meet the recommended guidelines for resistance-based exercise. Future research is needed to establish whether interventions including resistance-based exercise can improve health and fatigue levels in this population.

Number of Directional Changes Alters the Physiological, Perceptual, and Neuromuscular Responses of Netball Players During Intermittent Shuttle Running.

This study investigated whether an increased number of changes in direction altered the metabolic, cardiovascular, perceptual, and neuromuscular responses to intermittent shuttle running (ISR). Using a randomized crossover design, 10 female netball players completed 30 minutes of ISR over a 10-m (ISR10) and 20-m (ISR20) linear course. Measures of expired air, heart rate (HR), rating of perceived exertion, blood lactate concentration ([BLa]), and peak torque of knee extensors and flexors were measured. Differences (%change ± 90% CL) in VO2 (1.5 ± 5.6%) was unclear between conditions, whereas HR was possibly higher (1.5 ± 2.5%) and [BLa] very likely lower in ISR20 compared with ISR10 (-32.7 ± 9.9%). Rating of perceived exertion was likely lower in the ISR20 compared with the ISR10 condition at 15 (-5.0 ± 5.0%) and most likely lower at 30 minutes (-9.4 ± 2.0%). Sprint times over 20 m were likely slower during ISR20 at mid (3.9 ± 3.2%) but unclear after (2.1 ± 5.4%). Changes in muscle function were not different between ISR10 and ISR20 conditions for knee extension (-0.2 ± 0.9%) but were likely different for knee flexion (-5.7 ± 4.9%). More directional changes during shuttle running increase the physiological and perceptual load on female athletes, which also cause a greater reduction in knee extensor torque. These findings have implications for the effective conditioning and injury prevention of female team sport athletes.