Non-SARS-CoV-2 Respiratory Viruses in Athletes at Major Winter Sport Events, 2021 and 2022.

We performed prospective studies on respiratory viral infections among Team Finland participants during the 2021 Oberstdorf World Ski Championships and the 2022 Beijing Olympic Games. We enrolled 73 athletes and 110 staff members. Compared with similar studies we conducted before the COVID-19 pandemic, illnesses and virus detections dropped by 10-fold.

Risk factors associated with acute respiratory illnesses in athletes: a systematic review by a subgroup of the IOC consensus on 'acute respiratory illness in the athlete'.

OBJECTIVE: To review risk factors associated with acute respiratory illness (ARill) in athletes, including non-infectious ARill and suspected or confirmed acute respiratory infections (ARinf). DESIGN: Systematic review. DATA SOURCES: Electronic databases: PubMed-Medline, EbscoHost and Web of Science. ELIGIBILITY CRITERIA: Original research articles published between January 1990 and July 2020 in English were searched for prospective and retrospective full text studies that reported quantitative data on risk factors associated with ARill/ARinf in athletes, at any level of performance (elite/non-elite), aged 15-65 years. RESULTS: 48 studies (n=19 390 athletes) were included in the study. Risk factors associated with ARill/ARinf were: increased training monotony, endurance training programmes, lack of tapering, training during winter or at altitude, international travel and vitamin D deficits. Low tear-(SIgA) and salivary-(IgA) were immune biomarkers associated with ARill/ARinf. CONCLUSIONS: Modifiable training and environmental risk factors could be considered by sports coaches and athletes to reduce the risk of ARill/ARinf. Clinicians working with athletes can consider assessing and treating specific nutritional deficiencies such as vitamin D. More research regarding the role and clinical application of measuring immune biomarkers in athletes at high risk of ARill/ARinf is warranted. PROSPERO REGISTRATION NUMBER: CRD42020160928.

Incidence of acute respiratory illnesses in athletes: a systematic review and meta-analysis by a subgroup of the IOC consensus on 'acute respiratory illness in the athlete'.

OBJECTIVE: To determine the incidence of acute respiratory illness (ARill) in athletes and by method of diagnosis, anatomical classification, ages, levels of performance and seasons. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases: PubMed-Medline, EbscoHost and Web of Science. ELIGIBILITY CRITERIA: Original research articles published between January 1990 and July 2020 in English reporting the incidence of ARill in athletes, at any level of performance (elite/non-elite), aged 15-65 years. RESULTS: Across all 124 studies (n=1 28 360 athletes), the incidence of ARill, estimated by dividing the number of cases by the total number of athlete days, was 4.7 (95% CI 3.9 to 5.7) per 1000 athlete days. In studies reporting acute respiratory infections (ARinf; suspected and confirmed) the incidence was 4.9 (95% CI 4.0 to 6.0), which was similar in studies reporting undiagnosed ARill (3.7; 95% CI 2.1 to 6.7). Incidences of 5.9 (95% CI 4.8 to 7.2) and 2.8 (95% CI 1.8 to 4.5) were found for studies reporting upper ARinf and general ARinf (upper or lower), respectively. The incidence of ARinf was similar across the different methods to diagnose ARinf. A higher incidence of ARinf was found in non-elite (8.7; 95% CI 6.1 to 12.5) vs elite athletes (4.2; 95% CI 3.3 to 5.3). SUMMARY/CONCLUSIONS: These findings suggest: (1) the incidence of ARill equates to approximately 4.7 per athlete per year; (2) the incidence of upper ARinf was significantly higher than general (upper/lower) ARinf; (3) elite athletes have a lower incidence of ARinf than non-elite athletes; (4) if pathogen identification is not available, physicians can confidently use validated questionnaires and checklists to screen athletes for suspected ARinf. For future studies, we recommend that a clear diagnosis of ARill is reported. PROSPERO REGISTRATION NUMBER: CRD42020160472.

Glucocorticoids in elite sport: current status, controversies and innovative management strategies-a narrative review.

The use of systemic glucocorticoids (GCs), as well as local injections, continues to be a controversial issue in the sport/anti-doping community. There is widespread and legitimate use of GCs for numerous health conditions, yet there are concerns about side effects and the possibility of enhanced athletic performance in limited settings. This is compounded by the uncertainty regarding the prevalence of GC use, mechanisms underlying physiological effects and complex pharmacokinetics of different formulations. While WADA continues to promote research in this complex area, some international sporting federations, major event organisers and professional sports leagues have introduced innovative rules such as needle policies, mandatory rest periods and precompetition guidelines to promote judicious use of GCs, focusing on athlete health and supervision of medical personnel. These complementary sport-specific rules are helping to ensure the appropriate use of GCs in athletes where overuse is a particular concern. Where systemic GCs are medically necessary, Therapeutic Use Exemptions (TUEs) may be granted after careful evaluation by TUE Committees based on specific and strict criteria. Continued vigilance and cooperation between physicians, scientists and anti-doping organisations is essential to ensure that GC use in sport respects not only principles of fairness and adherence to the rules but also promotes athlete health and well-being. The purpose of this narrative review is to summarise the use and management of GCs in sport illustrating several innovative programmes by sport leagues and federations.

Common cold in Team Finland during 2018 Winter Olympic Games (PyeongChang): epidemiology, diagnosis including molecular point-of-care testing (POCT) and treatment.

OBJECTIVES: The common cold is the main cause of medical time loss in elite sport. Rapid diagnosis has been a challenge that may be amenable to molecular point-of-care testing (POCT). METHODS: We performed a prospective observational study of the common cold in Team Finland during the 2018 Winter Olympic Games. There were 44 elite athletes and 68 staff members. The chief physician recorded the symptoms of the common cold daily on a standardised form. Two nasal swabs were taken at the onset of symptoms. One swab was analysed within 45 min using a molecular POCT for respiratory syncytial virus and influenza A and B viruses. After the Games, the other swab was tested for 16 possible causative respiratory viruses using PCR in laboratory-based testing. RESULTS: 20 out of 44 (45%) athletes and 22 out of 68 (32%) staff members experienced symptoms of the common cold during a median stay of 21 days. Eleven (26%) samples tested virus-positive using POCT. All subjects with influenza (n=6) and 32 close contacts were treated with oseltamivir. The aetiology of the common cold was finally detected in 75% of the athletes and 68 % of the staff members. Seven virus clusters were identified. They were caused by coronaviruses 229E, NL63 and OC43, influenza B virus, respiratory syncytial virus A, rhinovirus and human metapneumovirus. The virus infections spread readily within the team, most commonly within the same sport discipline. CONCLUSIONS: The cold was indeed a common illness in Team Finland during the Winter Olympic Games. POCT proved to be clinically valuable, especially for influenza. The aetiology of the common cold was identified in most cases.

Beyond Menstrual Dysfunction: Does Altered Endocrine Function Caused by Problematic Low Energy Availability Impair Health and Sports Performance in Female Athletes?

Low energy availability, particularly when problematic (i.e., prolonged and/or severe), has numerous negative consequences for health and sports performance as characterized in relative energy deficiency in sport. These consequences may be driven by disturbances in endocrine function, although scientific evidence clearly linking endocrine dysfunction to decreased sports performance and blunted or diminished training adaptations is limited. We describe how low energy availability-induced changes in sex hormones manifest as menstrual dysfunction and accompanying hormonal dysfunction in other endocrine axes that lead to adverse health outcomes, including negative bone health, impaired metabolic activity, undesired outcomes for body composition, altered immune response, problematic cardiovascular outcomes, iron deficiency, as well as impaired endurance performance and force production, all of which ultimately may influence athlete health and performance. Where identifiable menstrual dysfunction indicates hypothalamic-pituitary-ovarian axis dysfunction, concomitant disturbances in other hormonal axes and their impact on the athlete's health and sports performance must be recognized as well. Given that the margin between podium positions and "losing" in competitive sports can be very small, several important questions regarding low energy availability, endocrinology, and the mechanisms behind impaired training adaptations and sports performance have yet to be explored.

International biathlon season during the COVID-19 pandemic was based on frequent on-site PCR-testing protocol with rapid result management.

The resumption of professional sports during the COVID-19 pandemic has been described in team sports but less in individual sports. The International Biathlon Union implemented a COVID-19 concept for the 2020-2021 season aimed to mitigate the risks of transmission by rules designated for the professional biathlon environment. The "bubble" model was based on regular reverse transcript polymerase chain reaction (PCR) testing with rapid results and efficient result management protocol. The objective of this study was report incidence and transmission of SARS-CoV-2 among professional biathletes and staff undergoing frequent PCR testing and risk reduction measures during the international season 2020-2021. The efficiency of risk mitigation measures was also evaluated based on the incidence data. During the 4-month season, altogether 22,182 SARS-CoV-2 PCR tests were conducted on all individuals participating in international biathlon season (athletes, team staff and organizing committee). Ninety-six (0.4%) PCR tests were positive and 30% of the positive PCR tests were considered "persistent positive" following recovery from a recent COVID-19 infection. No transmission events were detected following contact with "persistent positive" cases during the season. A great majority of the positive PCR tests were recorded during the first days after arrival in the "bubble", often in the first entry test taken by the on-site laboratory. In conclusion, a "bubble model" based on frequent PCR testing and hygiene rules was efficient in keeping the infection rate low. The competition activity including international travel was safe, and most of the infections seemed to originate from outside of the "bubble".

Ketogenic diet slows down mitochondrial myopathy progression in mice.

Mitochondrial dysfunction is a major cause of neurodegenerative and neuromuscular diseases of adult age and of multisystem disorders of childhood. However, no effective treatment exists for these progressive disorders. Cell culture studies suggested that ketogenic diet (KD), with low glucose and high fat content, could select against cells or mitochondria with mutant mitochondrial DNA (mtDNA), but proper patient trials are still lacking. We studied here the transgenic Deletor mouse, a disease model for progressive late-onset mitochondrial myopathy, accumulating mtDNA deletions during aging and manifesting subtle progressive respiratory chain (RC) deficiency. We found that these mice have widespread lipidomic and metabolite changes, including abnormal plasma phospholipid and free amino acid levels and ketone body production. We treated these mice with pre-symptomatic long-term and post-symptomatic shorter term KD. The effects of the diet for disease progression were followed by morphological, metabolomic and lipidomic tools. We show here that the diet decreased the amount of cytochrome c oxidase negative muscle fibers, a key feature in mitochondrial RC deficiencies, and prevented completely the formation of the mitochondrial ultrastructural abnormalities in the muscle. Furthermore, most of the metabolic and lipidomic changes were cured by the diet to wild-type levels. The diet did not, however, significantly affect the mtDNA quality or quantity, but rather induced mitochondrial biogenesis and restored liver lipid levels. Our results show that mitochondrial myopathy induces widespread metabolic changes, and that KD can slow down progression of the disease in mice. These results suggest that KD may be useful for mitochondrial late-onset myopathies.

Mitochondrial myopathy induces a starvation-like response.

Mitochondrial respiratory chain (RC) deficiency is among the most common causes of inherited metabolic disease, but its physiological consequences are poorly characterized. We studied the skeletal muscle gene expression profiles of mice with late-onset mitochondrial myopathy. These animals express a dominant patient mutation in the mitochondrial replicative helicase Twinkle, leading to accumulation of multiple mtDNA deletions and progressive subtle RC deficiency in the skeletal muscle. The global gene expression pattern of the mouse skeletal muscle showed induction of pathways involved in amino acid starvation response and activation of Akt signaling. Furthermore, the muscle showed induction of a fasting-related hormone, fibroblast growth factor 21 (Fgf21). This secreted regulator of lipid metabolism was also elevated in the mouse serum, and the animals showed widespread changes in their lipid metabolism: small adipocyte size, low fat content in the liver and resistance to high-fat diet. We propose that RC deficiency induces a mitochondrial stress response, with local and global changes mimicking starvation, in a normal nutritional state. These results may have important implications for understanding the metabolic consequences of mitochondrial myopathies.

Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice.

Defects of mitochondrial DNA (mtDNA) maintenance have recently been associated with inherited neurodegenerative and muscle diseases and the aging process. Twinkle is a nuclear-encoded mtDNA helicase, dominant mutations of which cause adult-onset progressive external ophthalmoplegia (PEO) with multiple mtDNA deletions. We have generated transgenic mice expressing mouse Twinkle with PEO patient mutations. Multiple mtDNA deletions accumulate in the tissues of these mice, resulting in progressive respiratory dysfunction and chronic late-onset mitochondrial disease starting at 1 year of age. The muscles of the mice faithfully replicate all of the key histological, genetic, and biochemical features of PEO patients. Furthermore, the mice have progressive deficiency of cytochrome c oxidase in distinct neuronal populations. These "deletor" mice do not, however, show premature aging, indicating that subtle accumulation of mtDNA deletions and progressive respiratory chain dysfunction are not sufficient to accelerate aging. This model is a valuable tool for therapy development and testing for adult-onset mitochondrial disorders.