Long COVID: Mechanismen, Risikofaktoren und Genesung

Long COVID, die lang anhaltende Krankheit und Erschöpfung, die bei einem kleinen Teil der SARS-CoV-2-Infizierten auftritt, stellt eine zunehmende Belastung für die Betroffenen und die Gesellschaft dar. Eine virtuelle Tagung der Physiological Society im Februar 2022 brachte Kliniker und Forscher zusammen, um das aktuelle Verständnis der Mechanismen, Risikofaktoren und Genesung nach Long COVID zu erörtern. In dieser Übersichtsarbeit werden die Themen behandelt, die sich aus dieser Tagung ergeben haben. Die Übersichtsarbeit befasst sich mit der Natur von Long COVID, untersucht den Zusammenhang mit anderen postviralen Erkrankungen wie der myalgischen Enzephalomyelitis/dem chronischen Erschöpfungssyndrom und zeigt auf, wie die Forschung zu Long COVID helfen kann, Patienten mit allen möglichen postviralen Syndromen besser zu unterstützen. Die Forschung zu Long COVID hat besonders rasche Fortschritte bei Bevölkerungsgruppen gemacht, die ihre körperliche Leistungsfähigkeit routinemäßig überwachen, insbesondere beim Militär und bei Leistungssportlern. In der Übersichtsarbeit wird hervorgehoben, inwiefern das hohe Niveau von Diagnose, Intervention und Erfolgskontrolle in diesen aktiven Bevölkerungsgruppen Informationen über Managementstrategien für die Allgemeinbevölkerung liefern kann. Anschließend wird untersucht, wie eine Schlüsselkomponente der Leistungsüberwachung bei diesen aktiven Bevölkerungsgruppen, das kardiopulmonale Training, Long-COVID-bedingte Veränderungen in der Physiologie aufdeckt − einschließlich Veränderungen der peripheren Muskelfunktion, der ventilatorischen Ineffizienz und der autonomen Dysfunktion. Das Wesen und die Auswirkungen der Dysautonomie werden im Zusammenhang mit dem posturalen orthostatischen Tachykardiesyndrom, der Fatigue und den Behandlungsstrategien, die darauf abzielen, der Überaktivierung des Sympathikus durch Stimulation des Vagusnervs entgegenzuwirken, erörtert. Anschließend untersuchen wir die Mechanismen, die den Symptomen von Long COVID zugrunde liegen. Dabei konzentrieren wir uns auf die gestörte Sauerstoffversorgung durch Mikrokoagulation und die Störung des zellulären Energiestoffwechsels, bevor wir Behandlungsstrategien betrachten, die direkt oder indirekt auf diese Mechanismen abzielen. Dazu gehören ein fernbetreutes Atemmuskeltraining und integrierte Versorgungspfade, die Rehabilitation und medikamentöse Interventionen mit der Erforschung des Zugangs zur Long-COVID-Versorgung in verschiedenen Bevölkerungsgruppen kombinieren. Insgesamt zeigt diese Übersichtsarbeit, wie im Rahmen der physiologischen Forschung die bei Long COVID auftretenden Veränderungen aufgedeckt werden und wie verschiedene therapeutische Strategien zur Bekämpfung dieser Erkrankung entwickelt und getestet werden.

Emission rates, size distributions, and generation mechanism of oral respiratory droplets

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought renewed attention to respiratory aerosol and droplet generation. While many studies have robustly quantified aerosol (<10 µm diameter) number and mass exhalation rates, fewer studies have explored larger droplet generation. This study quantifies respiratory droplets (>20 µm diameter) generated by a cohort of 76 adults and children using a water-sensitive paper droplet deposition approach. Unvoiced and voiced activities spanning different levels of loudness, different lengths of sustained phonation, and a specific manner of articulation in isolation were investigated. We find that oral articulation drives >20 µm droplet generation, with breathing generating virtually no droplets and speaking and singing generating on the order of 250 droplets min−1. Lip trilling, which requires extensive oral articulation, generated the most droplets, whereas shouting "Hey,” which requires minimal oral articulation, generated relatively few droplets. Droplet size distributions were all broadly consistent, and no significant differences between the children and adult cohorts were identified. By comparing the aerosol and droplet emissions for the same participants, the full size distribution of respiratory aerosol (0.5–1000 µm) is reported. Although <10 µm aerosol dominates the number concentration, >20 µm droplets dominate the mass concentration. Accurate quantification of aerosol concentrations in the 10–70 μm size range remains very challenging;more robust aerosol analysis approaches are needed to characterize this size range.

Long COVID: mechanisms, risk factors and recovery.

NEW FINDINGS: What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies. ABSTRACT: Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance - namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology - including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

Respiratory complications following COVID-19 in athletic populations: A narrative review.

Athletes typically experience a mild-to-moderate, self-limiting illness following infection with the novel severe acute respiratory syndrome coronavirus 2. Some athletes, however, can develop prolonged symptoms, with breathlessness, cough, and chest tightness impacting return to training and competition. In athletes with persistent cardiopulmonary symptoms following COVID-19, focus is usually placed on the identification and characterization of cardiac complications, such as myocarditis. In this review, we focus on summarizing the literature assessing pulmonary complications and physiological consequences associated with COVID-19 illness in athletes. The review also provides recommendations for clinical assessment of the athlete with pulmonary issues following COVID-19 and directions for future research.

Emission Rates, Size Distributions, and Generation Mechanism of Oral Respiratory Droplets

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought renewed attention to respiratory aerosol and droplet generation. While many studies have robustly quantified aerosol (<10 µm diameter) number and mass exhalation rates, fewer studies have explored larger droplet generation. This study quantifies respiratory droplets (>20 µm diameter) generated by a cohort of 76 adults and children using a water-sensitive paper droplet deposition approach. Unvoiced and voiced activities spanning different levels of loudness, different lengths of sustained phonation, and a specific manner of articulation in isolation were investigated. We find that oral articulation drives >20 µm droplet generation, with breathing generating virtually no droplets and speaking and singing generating on the order of 250 droplets min−1. Lip trilling, which requires extensive oral articulation, generated the most droplets, whereas shouting "Hey”, which requires minimal oral articulation, generated relatively few droplets. Droplet size distributions were all broadly consistent, and no significant differences between the children and adult cohorts were identified. By comparing the aerosol and droplet emissions for the same participants, the full size distribution of respiratory aerosol (0.5-1000 µm) is reported. Although <10 µm aerosol dominates the number concentration, >20 µm droplets dominate the mass concentration. Accurate quantification of aerosol concentrations in the 10-70 μm size range remains very challenging;more robust aerosol analysis approaches are needed to characterize this size range. [ FROM AUTHOR]

Persistent isolated impairment of gas transfer following COVID-19 pneumonitis relates to perfusion defects on dual-energy computed tomography.

A novel iodine perfusion score correlates with breathlessness and D LCO in patients post-#COVID19 without obvious interstitial disease on CT, suggesting that lung perfusion assessment may be useful in patients without another cause of dyspnoea https://bit.ly/3U6E2f5.

International Olympic Committee (IOC) consensus statement on acute respiratory illness in athletes part 1: acute respiratory infections.

Acute illnesses affecting the respiratory tract are common and form a significant component of the work of Sport and Exercise Medicine (SEM) clinicians. Acute respiratory illness (ARill) can broadly be classified as non-infective ARill and acute respiratory infections (ARinf). The aim of this consensus is to provide the SEM clinician with an overview and practical clinical approach to ARinf in athletes. The International Olympic Committee (IOC) Medical and Scientific Commission appointed an international consensus group to review ARill (non-infective ARill and ARinf) in athletes. Six subgroups of the IOC Consensus group were initially established to review the following key areas of ARill in athletes: (1) epidemiology/risk factors for ARill, (2) ARinf, (3) non-infective ARill including ARill due to environmental exposure, (4) acute asthma and related conditions, (5) effects of ARill on exercise/sports performance, medical complications/return-to-sport and (6) acute nasal/vocal cord dysfunction presenting as ARill. Several systematic and narrative reviews were conducted by IOC consensus subgroups, and these then formed the basis of sections in the consensus documents. Drafting and internal review of sections were allocated to 'core' members of the consensus group, and an advanced draft of the consensus document was discussed during a meeting of the main consensus core group in Lausanne, Switzerland on 11 to 12 October 2021. Final edits were completed after the meeting. This consensus document (part 1) focusses on ARinf, which accounts for the majority of ARill in athletes. The first section of this consensus proposes a set of definitions and classifications of ARinf in athletes to standardise future data collection and reporting. The remainder of the consensus paper examines a wide range of clinical considerations related to ARinf in athletes: epidemiology, risk factors, pathology/pathophysiology, clinical presentation and diagnosis, management, prevention, medical considerations, risks of infection during exercise, effects of infection on exercise/sports performance and return-to-sport guidelines.

Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.

The effects of acute respiratory illness on exercise and sports performance outcomes in athletes - A systematic review by a subgroup of the IOC consensus group on "Acute respiratory illness in the athlete".

Acute respiratory infections (ARinf) are common in athletes, but their effects on exercise and sports performance remain unclear. This systematic review aimed to determine the acute (short-term) and longer-term effects of ARinf, including SARS-CoV-2 infection, on exercise and sports performance outcomes in athletes. Data sources searched included PubMed, Web of Science and EBSCOhost, from January 1990 to 31 December 2021. Eligibility criteria included original research studies published in English, measuring exercise and/or sports performance outcomes in athletes/physically active/military aged 15-65 years with ARinf. Information regarding the study cohort, diagnostic criteria, illness classification and quantitative data on the effect on exercise/sports performance were extracted. Database searches identified 1707 studies. After full-text screening, 17 studies were included (n = 7793). Outcomes were acute or longer-term effects on exercise (cardiovascular or pulmonary responses), or sports performance (training modifications, change in standardised point scoring systems, running biomechanics, match performance or ability to start/finish an event). There was substantial methodological heterogeneity between studies. ARinf was associated with acute decrements in sports performance outcomes (four studies) and pulmonary function (three studies), but minimal effects on cardiorespiratory endurance (seven studies in mild ARinf). Longer-term detrimental effects of ARinf on sports performance (six studies) were divided. Training mileage, overall training load, standardised sports performance-dependent points and match play can be affected over time. Despite few studies, there is a trend towards impairment in acute and longer-term exercise and sports outcomes after ARinf in athletes. Future research should consider a uniform approach to explore relationships between ARinf and exercise/sports performance.PROSPERO (CRD42020159259) HighlightsCardiorespiratory endurance is largely unaffected by recent mild SARS-CoV-2 infection and upper ARinf (rhinovirus) infection, however more severe ARinf is associated with a negative impact on exercise and sports performance.An upper ARinf (rhinovirus) and SARS-CoV-2 infection caused marked reductions in pulmonary function tests (FEV1.0/FVC), with greater reductions observed in more severe ARinf. However, the results remained within normal ranges.Self-reported training ability and training capacity can be reduced during an upper ARinf, and an ARinf with fever could alter running kinematics.Training mileage and overall training load can be impaired over time post-ARinf. Analysis of initial studies indicates a trend for a reduction in standardised sports performance-dependent points in athletes with respiratory infection.

A comparison of respiratory particle emission rates at rest and while speaking or exercising.

Background: The coronavirus disease-19 (COVID-19) pandemic led to the prohibition of group-based exercise and the cancellation of sporting events. Evaluation of respiratory aerosol emissions is necessary to quantify exercise-related transmission risk and inform mitigation strategies. Methods: Aerosol mass emission rates are calculated from concurrent aerosol and ventilation data, enabling absolute comparison. An aerodynamic particle sizer (0.54-20 µm diameter) samples exhalate from within a cardiopulmonary exercise testing mask, at rest, while speaking and during cycle ergometer-based exercise. Exercise challenge testing is performed to replicate typical gym-based exercise and very vigorous exercise, as determined by a preceding maximally exhaustive exercise test. Results: We present data from 25 healthy participants (13 males, 12 females; 36.4 years). The size of aerosol particles generated at rest and during exercise is similar (unimodal ~0.57-0.71 µm), whereas vocalization also generated aerosol particles of larger size (i.e. was bimodal ~0.69 and ~1.74 µm). The aerosol mass emission rate during speaking (0.092 ng s-1; minute ventilation (VE) 15.1 L min-1) and vigorous exercise (0.207 ng s-1, p = 0.726; VE 62.6 L min-1) is similar, but lower than during very vigorous exercise (0.682 ng s-1, p < 0.001; VE 113.6 L min-1). Conclusions: Vocalisation drives greater aerosol mass emission rates, compared to breathing at rest. Aerosol mass emission rates in exercise rise with intensity. Aerosol mass emission rates during vigorous exercise are no different from speaking at a conversational level. Mitigation strategies for airborne pathogens for non-exercise-based social interactions incorporating vocalisation, may be suitable for the majority of exercise settings. However, the use of facemasks when exercising may be less effective, given the smaller size of particles produced.

Clinical patterns, recovery time and prolonged impact of COVID-19 illness in international athletes: the UK experience.

OBJECTIVES: To report COVID-19 illness pattern, symptom duration and time loss in UK elite athletes. METHODS: Observational, clinical and database review of athletes with symptomatic COVID-19 illness managed within the UK Sports Institutes. Athletes were classified as confirmed (positive SARS-CoV-2 PCR or antibody tests) or probable (consistent clinical features) COVID-19. Clinical presentation was characterised by the predominant symptom focus (eg, upper or lower respiratory illness). Time loss was defined as days unavailable for full sport participation and comparison was made with a 2016-2019 respiratory illness dataset from the same surveillance system. RESULTS: Between 24 February 2020 and 18 January 2021, 147 athletes (25 Paralympic (17%)) with mean (SD) age 24.7 (5.2) years, 37% female, were diagnosed with COVID-19 (76 probable, 71 confirmed). Fatigue was the most prevalent symptom (57%), followed by dry cough (50%) and headache (46%). The median (IQR) symptom duration was 10 (6-17) days but 14% reported symptoms >28 days. Median time loss was 18 (12-30) days, with 27% not fully available >28 days from initial date of infection. This was greater than our historical non-COVID respiratory illness comparator; 6 days, 0-7 days (p<0.001) and 4% unavailable at 28 days. A lower respiratory phenotype (ie, including dyspnoea±chest pain±cough±fever) was present in 18% and associated with a higher relative risk of prolonged symptoms risk ratio 3.0 (95% CI: 1.4 to 6.5) and time loss 2.1 (95% CI: 1.2 to 3.5). CONCLUSIONS: In this cohort, COVID-19 largely resulted in a mild, self-limiting illness. The presence of lower respiratory tract features was associated with prolonged illness and a delayed return to sport.

Pulmonary function and COVID-19.

In people recovering from COVID-19, there is concern regarding potential long-term pulmonary sequelae and associated impairment of functional capacity. Data published thus far indicate that spirometric indices appear to be generally well preserved, but that a defect in diffusing capacity (DLco) is a prevalent abnormality identified on follow-up lung function; present in 20-30% of those with mild to moderate disease and 60% in those with severe disease. Reductions in total lung capacity were commonly reported. Functional capacity is also often impaired, with data now starting to emerge detailing walk test and cardiopulmonary exercise test outcome at follow-up. In this review, we evaluate the published evidence in this area, to summarise the impact of COVID-19 infection on pulmonary function and relate this to the clinico-radiological findings and disease severity.

Symptom cluster is associated with prolonged return-to-play in symptomatic athletes with acute respiratory illness (including COVID-19): a cross-sectional study-AWARE study I.

BACKGROUND: There are no data relating symptoms of an acute respiratory illness (ARI) in general, and COVID-19 specifically, to return to play (RTP). OBJECTIVE: To determine if ARI symptoms are associated with more prolonged RTP, and if days to RTP and symptoms (number, type, duration and severity) differ in athletes with COVID-19 versus athletes with other ARI. DESIGN: Cross-sectional descriptive study. SETTING: Online survey. PARTICIPANTS: Athletes with confirmed/suspected COVID-19 (ARICOV) (n=45) and athletes with other ARI (ARIOTH) (n=39). METHODS: Participants recorded days to RTP and completed an online survey detailing ARI symptoms (number, type, severity and duration) in three categories: 'nose and throat', 'chest and neck' and 'whole body'. We report the association between symptoms and RTP (% chance over 40 days) and compare the days to RTP and symptoms (number, type, duration and severity) in ARICOV versus ARIOTH subgroups. RESULTS: The symptom cluster associated with more prolonged RTP (lower chance over 40 days; %) (univariate analysis) was 'excessive fatigue' (75%; p<0.0001), 'chills' (65%; p=0.004), 'fever' (64%; p=0.004), 'headache' (56%; p=0.006), 'altered/loss sense of smell' (51%; p=0.009), 'Chest pain/pressure' (48%; p=0.033), 'difficulty in breathing' (48%; p=0.022) and 'loss of appetite' (47%; p=0.022). 'Excessive fatigue' remained associated with prolonged RTP (p=0.0002) in a multiple model. Compared with ARIOTH, the ARICOV subgroup had more severe disease (greater number, more severe symptoms) and more days to RTP (p=0.0043). CONCLUSION: Symptom clusters may be used by sport and exercise physicians to assist decision making for RTP in athletes with ARI (including COVID-19).

UK consensus statement on the diagnosis of inducible laryngeal obstruction in light of the COVID-19 pandemic.

Prior to the COVID-19 pandemic, laryngoscopy was the mandatory gold standard for the accurate assessment and diagnosis of inducible laryngeal obstruction. However, upper airway endoscopy is considered an aerosol-generating procedure in professional guidelines, meaning routine procedures are highly challenging and the availability of laryngoscopy is reduced. In response, we have convened a multidisciplinary panel with broad experience in managing this disease and agreed a recommended strategy for presumptive diagnosis in patients who cannot have laryngoscopy performed due to pandemic restrictions. To maintain clinical standards whilst ensuring patient safety, we discuss the importance of triage, information gathering, symptom assessment and early review of response to treatment. The consensus recommendations will also be potentially relevant to other future situations where access to laryngoscopy is restricted, although we emphasize that this investigation remains the gold standard.

Cardiorespiratory considerations for return-to-play in elite athletes after COVID-19 infection: a practical guide for sport and exercise medicine physicians.

SARS-CoV-2 is the causative virus responsible for the COVID-19 pandemic. This pandemic has necessitated that all professional and elite sport is either suspended, postponed or cancelled altogether to minimise the risk of viral spread. As infection rates drop and quarantine restrictions are lifted, the question how athletes can safely resume competitive sport is being asked. Given the rapidly evolving knowledge base about the virus and changing governmental and public health recommendations, a precise answer to this question is fraught with complexity and nuance. Without robust data to inform policy, return-to-play (RTP) decisions are especially difficult for elite athletes on the suspicion that the COVID-19 virus could result in significant cardiorespiratory compromise in a minority of afflicted athletes. There are now consistent reports of athletes reporting persistent and residual symptoms many weeks to months after initial COVID-19 infection. These symptoms include cough, tachycardia and extreme fatigue. To support safe RTP, we provide sport and exercise medicine physicians with practical recommendations on how to exclude cardiorespiratory complications of COVID-19 in elite athletes who place high demand on their cardiorespiratory system. As new evidence emerges, guidance for a safe RTP should be updated.