Uncovering a neurological protein signature for severe COVID-19.

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has sparked a global pandemic with severe complications and high morbidity rate. Neurological symptoms in COVID-19 patients, and neurological sequelae post COVID-19 recovery have been extensively reported. Yet, neurological molecular signature and signaling pathways that are affected in the central nervous system (CNS) of COVID-19 severe patients remain still unknown and need to be identified. Plasma samples from 49 severe COVID-19 patients, 50 mild COVID-19 patients, and 40 healthy controls were subjected to Olink proteomics analysis of 184 CNS-enriched proteins. By using a multi-approach bioinformatics analysis, we identified a 34-neurological protein signature for COVID-19 severity and unveiled dysregulated neurological pathways in severe cases. Here, we identified a new neurological protein signature for severe COVID-19 that was validated in different independent cohorts using blood and postmortem brain samples and shown to correlate with neurological diseases and pharmacological drugs. This protein signature could potentially aid the development of prognostic and diagnostic tools for neurological complications in post-COVID-19 convalescent patients with long term neurological sequelae.

Training Practices of Football Players During the Early COVID-19 Lockdown Worldwide.

The COVID-19 lockdown challenged the training options of athletes worldwide, including players from the most popular sport globally, football/soccer. PURPOSE: The authors explored the training practices of football players worldwide during the COVID-19 lockdown. METHODS: Football players (N = 2482, 30% professional, 22% semipro, and 48% amateur) completed an online survey (May-July 2020) on their training practices before versus during lockdown (March-June 2020). Questions were related to training frequency and session duration, as well as training knowledge and attitudes. RESULTS: Before lockdown, more professional (87%) than semipro (67%) and amateur (65%) players trained ≥5 sessions/wk, but this proportion decreased during the lockdown to 55%, 35%, and 42%, respectively. Players (80%-87%) trained ≥60 minutes before lockdown, but this proportion decreased to 45% in professionals, 43% in amateurs, and 36% in semipros during lockdown. At home, more than two-thirds of players had training space (73%) and equipment (66%) for cardiorespiratory training, while availability of equipment for technical and strength training was <50% during lockdown. Interactions between coach/trainer and player were more frequent (ie, daily) among professional (27%) than amateur (11%) and semipro (17%) players. Training load monitoring, albeit limited, was mostly performed by fitness coaches, more so with professionals (35%) than amateurs (13%) and semipros (17%). The players' training knowledge and attitudes/beliefs toward training were relatively modest (50%-59%). CONCLUSION: COVID-19 lockdown negatively affected training practices of football players worldwide, especially amateurs and semipros, for example, in training frequency, duration, intensity, technical, recovery, and other fitness training and coaching-related aspects. During lockdown-like situations, players should be monitored closely and provided appropriate support to facilitate their training.

Athlete level, sport-type, and gender influences on training, mental health, and sleep during the early COVID-19 lockdown in Malaysia.

Purpose: We evaluated the extent of changes in training practices, recovery, mental health, and sleep patterns of athletes during the early COVID-19 lockdown in a single country-cohort. Methods: A total of 686 athletes (59% male, 41% female; 9% World Class, 28% International, 29% National, 26% State, 8% Recreational) from 50 sports (45% individual, 55% team) in Malaysia completed an online, survey-based questionnaire study. The questions were related to training practices (including recovery and injury), mental health, and sleep patterns. Results: Relative to pre-lockdown, training intensity (-34%), frequency (-20%, except World-Class), and duration (-24%-59%, especially International/World-Class) were compromised, by the mandated lockdown. During the lockdown, more space/access (69%) and equipment (69%) were available for cardiorespiratory training, than technical and strength; and these resources favoured World-Class athletes. Most athletes trained for general strength/health (88%) and muscular endurance (71%); and some used innovative/digital training tools (World-Class 48% vs. lower classification-levels ≤34%). More World-Class, International, and National athletes performed strength training, plyometrics, and sport-specific technical skills with proper equipment, than State/Recreational athletes. More females (42%) sourced training materials from social media than males (29%). Some athletes (38%) performed injury prevention exercises; 18% had mild injuries (knees 29%, ankles 26%), and 18% received a medical diagnosis (International 31%). Lower-level athletes (e.g., State 44%) disclosed that they were mentally more vulnerable; and felt more anxious (36% vs. higher-levels 14%-21%). Sleep quality and quantity were "normal" (49% for both), "improved" (35% and 27%), and only 16% and 14% (respectively) stated "worsened" sleep. Conclusion: Lockdown compromised training-related practices, especially in lower-level athletes. Athletes are in need of assistance with training, and tools to cope with anxiety that should be tailored to individual country requirements during lockdown situations. In particular, goal-driven (even if it is at home) fitness training, psychological, financial, and lifestyle support can be provided to reduce the difficulties associated with lockdowns. Policies and guidelines that facilitate athletes (of all levels) to train regularly during the lockdown should be developed.

Ramadan intermittent fasting induced poorer training practices during the COVID-19 lockdown: A global cross-sectional study with 5529 athletes from 110 countries.

Ramadan intermittent fasting during the COVID-19 lockdown (RIFL) may present unique demands. We investigated training practices (i.e., training load and training times) of athletes, using pre-defined survey criteria/questions, during the 'first' COVID-19 lockdown, comparing RIFL to lockdown-alone (LD) in Muslim athletes. Specifically, a within-subject, survey-based study saw athletes (n = 5,529; from 110 countries/territories) training practices (comparing RIFL to LD) explored by comparative variables of: sex; age; continent; athlete classification (e.g., world-class); sport classification (e.g., endurance); athlete status (e.g., professional); and level of training knowledge and beliefs/attitudes (ranked as: good/moderate/poor). During RIFL (compared to LD), athlete perceptions (ranges presented given variety of comparative variables) of their training load decreased (46-62%), were maintained (31-48%) or increased (2-13%). Decreases (≥ 5%, p < 0.05) affected more athletes aged 30-39 years than those 18-29 years (60 vs 55%); more national than international athletes (59 vs 51%); more team sports than precision sports (59 vs 46%); more North American than European athletes (62 vs 53%); more semi-professional than professional athletes (60 vs 54%); more athletes who rated their beliefs/attitudes 'good' compared to 'poor' and 'moderate' (61 vs 54 and 53%, respectively); and more athletes with 'moderate' than 'poor' knowledge (58 vs 53%). During RIFL, athletes had different strategies for training times, with 13-29% training twice a day (i.e., afternoon and night), 12-26% at night only, and 18-36% in the afternoon only, with ranges depending on the comparative variables. Training loads and activities were altered negatively during RIFL compared to LD. It would be prudent for decision-makers responsible for RIFL athletes to develop programs to support athletes during such challenges.

COVID-19 Lockdown: A Global Study Investigating the Effect of Athletes' Sport Classification and Sex on Training Practices.

PURPOSE: To investigate differences in athletes' knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification. METHODS: Athletes (12,526; 66% male; 142 countries) completed an online survey (May-July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed. RESULTS: During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%-49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%-28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%). CONCLUSIONS: Changes in athletes' training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.

Ramadan Observance Exacerbated the Negative Effects of COVID-19 Lockdown on Sleep and Training Behaviors: A International Survey on 1,681 Muslim Athletes.

Objective: Disrupted sleep and training behaviors in athletes have been reported during the COVID-19 pandemic. We aimed at investigating the combined effects of Ramadan observance and COVID-19 related lockdown in Muslim athletes. Methods: From an international sample of athletes (n = 3,911), 1,681 Muslim athletes (from 44 countries; 25.1 ± 8.7 years, 38% females, 41% elite, 51% team sport athletes) answered a retrospective, cross-sectional questionnaire relating to their behavioral habits pre- and during- COVID-19 lockdown, including: (i) Pittsburgh sleep quality index (PSQI); (ii) insomnia severity index (ISI); (iii) bespoke questions about training, napping, and eating behaviors, and (iv) questions related to training and sleep behaviors during-lockdown and Ramadan compared to lockdown outside of Ramadan. The survey was disseminated predominately through social media, opening 8 July and closing 30 September 2020. Results: The lockdown reduced sleep quality and increased insomnia severity (both p < 0.001). Compared to non-Muslim (n = 2,230), Muslim athletes reported higher PSQI and ISI scores during-lockdown (both p < 0.001), but not pre-lockdown (p > 0.05). Muslim athletes reported longer (p < 0.001; d = 0.29) and later (p < 0.001; d = 0.14) daytime naps, and an increase in late-night meals (p < 0.001; d = 0.49) during- compared to pre-lockdown, associated with lower sleep quality (all p < 0.001). Both sleep quality (χ2 = 222.6; p < 0.001) and training volume (χ2 = 342.4; p < 0.001) were lower during-lockdown and Ramadan compared to lockdown outside of Ramadan in the Muslims athletes. Conclusion: Muslim athletes reported lower sleep quality and higher insomnia severity during- compared to pre-lockdown, and this was exacerbated by Ramadan observance. Therefore, further attention to Muslim athletes is warranted when a circadian disrupter (e.g., lockdown) occurs during Ramadan.

Lockdown Duration and Training Intensity Affect Sleep Behavior in an International Sample of 1,454 Elite Athletes.

Objective: To investigate the effect of 1) lockdown duration and 2) training intensity on sleep quality and insomnia symptoms in elite athletes. Methods: 1,454 elite athletes (24.1 ± 6.7 years; 42% female; 41% individual sports) from 40 countries answered a retrospective, cross-sectional, web-based questionnaire relating to their behavioral habits pre- and during- COVID-19 lockdown, including: 1) Pittsburgh sleep quality index (PSQI); 2) Insomnia severity index (ISI); bespoke questions about 3) napping; and 4) training behaviors. The association between dependent (PSQI and ISI) and independent variables (sleep, napping and training behaviors) was determined with multiple regression and is reported as semi-partial correlation coefficient squared (in percentage). Results: 15% of the sample spent < 1 month, 27% spent 1-2 months and 58% spent > 2 months in lockdown. 29% self-reported maintaining the same training intensity during-lockdown whilst 71% reduced training intensity. PSQI (4.1 ± 2.4 to 5.8 ± 3.1; mean difference (MD): 1.7; 95% confidence interval of the difference (95% CI): 1.6-1.9) and ISI (5.1 ± 4.7 to 7.7 ± 6.4; MD: 2.6; 95% CI: 2.3-2.9) scores were higher during-compared to pre-lockdown, associated (all p < 0.001) with longer sleep onset latency (PSQI: 28%; ISI: 23%), later bedtime (PSQI: 13%; ISI: 14%) and later preferred time of day to train (PSQI: 9%; ISI: 5%) during-lockdown. Those who reduced training intensity during-lockdown showed higher PSQI (p < 0.001; MD: 1.25; 95% CI: 0.87-1.63) and ISI (p < 0.001; MD: 2.5; 95% CI: 1.72-3.27) scores compared to those who maintained training intensity. Although PSQI score was not affected by the lockdown duration, ISI score was higher in athletes who spent > 2 months confined compared to those who spent < 1 month (p < 0.001; MD: 1.28; 95% CI: 0.26-2.3). Conclusion: Reducing training intensity during the COVID-19-induced lockdown was associated with lower sleep quality and higher insomnia severity in elite athletes. Lockdown duration had further disrupting effects on elite athletes' sleep behavior. These findings could be of relevance in future lockdown or lockdown-like situations (e.g., prolonged illness, injury, and quarantine after international travel).

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications.

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.

Regression Analysis of Perceived Stress among Elite Athletes from Changes in Diet, Routine and Well-Being: Effects of the COVID-19 Lockdown and "Bubble" Training Camps.

The COVID-19 pandemic has affected the lifestyles and training of elite athletes around the world. The detrimental effects of lockdown periods may vary among individuals, as well as among sports and sexes. This study investigated the changes in dietary habits, and the predictors of perceived stress during lockdown and a "bubble" training camp. This cross-sectional, online survey involved 76 elite and world-class athletes from six able-bodied sports and nine parasports, all of whom were involved in a 30-day "bubble" training camp. Questions were asked on socio-demographics, training routines and wellbeing, perceived stress, and dietary habits, pertaining to "normal" training (prelockdown), lockdown training, and "bubble" camp training periods. Changes in perceived stress were trivial to small during lockdown compared to "normal" training, and trivial to moderate during a "bubble" camp, compared to lockdown. Para-athletes, males, older athletes, less experienced athletes, married individuals, and specific ethnicities appeared to be more detrimentally affected (increased perceived stress) by lockdown. These negative experiences, however, were largely reversed during "bubble" camps. During lockdown, more athletes reported increased evening snack consumption (+8%), later meal-times (+6%), decreased fluid intake (-6%), and no breakfast (+7%). These changes were reversed during "bubble" camps (12-18% improvements). Sport classification accounted for 16% of the increased perceived stress (p = 0.001) during lockdown. Overall, socio-demographic factors, improvements in training routines, well-being, and dietary habits explained 28% of the decreased perceived stress during a "bubble" camp. In conclusion, better dietary habits, training routines and well-being have implications for reduced perceived stress. During lockdown, "bubble" camps may be beneficial, but this observation may be a case-by-case consideration, and short split "bubble" periods are recommended.

COVID-19 Lockdowns: A Worldwide Survey of Circadian Rhythms and Sleep Quality in 3911 Athletes from 49 Countries, with Data-Driven Recommendations.

OBJECTIVE: In a convenience sample of athletes, we conducted a survey of COVID-19-mediated lockdown (termed 'lockdown' from this point forward) effects on: (i) circadian rhythms; (ii) sleep; (iii) eating; and (iv) training behaviors. METHODS: In total, 3911 athletes [mean age: 25.1 (range 18-61) years, 1764 female (45%), 2427 team-sport (63%) and 1442 elite (37%) athletes] from 49 countries completed a multilingual cross-sectional survey including the Pittsburgh Sleep Quality Index and Insomnia Severity Index questionnaires, alongside bespoke questions about napping, training, and nutrition behaviors. RESULTS: Pittsburgh Sleep Quality Index (4.3 ± 2.4 to 5.8 ± 3.1) and Insomnia Severity Index (4.8 ± 4.7 to 7.2 ± 6.4) scores increased from pre- to during lockdown (p < 0.001). Pittsburgh Sleep Quality Index was predominantly influenced by sleep-onset latency (p < 0.001; + 29.8%), sleep efficiency (p < 0.001; - 21.1%), and total sleep time (p < 0.001; - 20.1%), whilst Insomnia Severity Index was affected by sleep-onset latency (p < 0.001; + 21.4%), bedtime (p < 0.001; + 9.4%), and eating after midnight (p < 0.001; + 9.1%). During lockdown, athletes reported fewer training sessions per week (- 29.1%; d = 0.99). Athletes went to bed (+ 75 min; 5.4%; d = 1.14) and woke up (+ 150 min; 34.5%; d = 1.71) later during lockdown with an increased total sleep time (+ 48 min; 10.6%; d = 0.83). Lockdown-mediated circadian disruption had more deleterious effects on the sleep quality of individual-sport athletes compared with team-sport athletes (p < 0.001; d = 0.41), elite compared with non-elite athletes (p = 0.028; d = 0.44) and older compared with younger (p = 0.008; d = 0.46) athletes. CONCLUSIONS: These lockdown-induced behavioral changes reduced sleep quality and increased insomnia in athletes. Data-driven and evidence-based recommendations to counter these include, but are not limited to: (i) early outdoor training; (ii) regular meal scheduling (whilst avoiding meals prior to bedtime and caffeine in the evening) with appropriate composition; (iii) regular bedtimes and wake-up times; and (iv) avoidance of long and/or late naps.

Training During the COVID-19 Lockdown: Knowledge, Beliefs, and Practices of 12,526 Athletes from 142 Countries and Six Continents.

OBJECTIVE: Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational) completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session duration before and during lockdown (March-June 2020). RESULTS: Overall, 85% of athletes wanted to "maintain training," and 79% disagreed with the statement that it is "okay to not train during lockdown," with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered "coaching by correspondence (remote coaching)" to be sufficient (highest amongst world-class athletes). During lockdown, < 40% were able to maintain sport-specific training (e.g., long endurance [39%], interval training [35%], weightlifting [33%], plyometric exercise [30%]) at pre-lockdown levels (higher among world-class, international, and national athletes), with most (83%) training for "general fitness and health maintenance" during lockdown. Athletes trained alone (80%) and focused on bodyweight (65%) and cardiovascular (59%) exercise/training during lockdown. Compared with before lockdown, most athletes reported reduced training frequency (from between five and seven sessions per week to four or fewer), shorter training sessions (from ≥ 60 to < 60 min), and lower sport-specific intensity (~ 38% reduction), irrespective of athlete classification. CONCLUSIONS: COVID-19-related lockdowns saw marked reductions in athletic training specificity, intensity, frequency, and duration, with notable within-sample differences (by athlete classification). Higher classification athletes had the strongest desire to "maintain" training and the greatest opposition to "not training" during lockdowns. These higher classification athletes retained training specificity to a greater degree than others, probably because of preferential access to limited training resources. More higher classification athletes considered "coaching by correspondence" as sufficient than did lower classification athletes. These lockdown-mediated changes in training were not conducive to maintenance or progression of athletes' physical capacities and were also likely detrimental to athletes' mental health. These data can be used by policy makers, athletes, and their multidisciplinary teams to modulate their practice, with a degree of individualization, in the current and continued pandemic-related scenario. Furthermore, the data may drive training-related educational resources for athletes and their multidisciplinary teams. Such upskilling would provide athletes with evidence to inform their training modifications in response to germane situations (e.g., COVID related, injury, and illness).