Anatomy of an American football game: Player-to-player contact before, during and after an NFL game in context of the 2020 COVID-19 pandemic.

OBJECTIVES: To quantify levels of potential exposure to SARS-CoV-2 surrounding a typical professional American football game, with a focus on interactions on-field between teammates and opposing players before, during, and immediately after competition. METHODS: We examined across-Club consecutive interactions ≥2 minutes within 6 feet [1.8 meters] between athletes on opposing Clubs for all 2020 NFL regular season games (n = 256). Cumulative interaction was measured for a representative subset (n = 119; 46%) of games. Wearable proximity tracking devices (Kinexon) were used to measure distance and duration of interactions; these data were combined with game schedule and Club rosters for analyses. Frequency and per-game mean, median, interquartile range for consecutive interactions ≥2/≥5 minutes and cumulative interactions ≥5/≥15 were described overall and stratified by pre-game, in-game, and post-game. RESULTS: Of the 1964 distinct player-to-opponent contacts ≥2 minutes in NFL regular season games, the majority (n = 1,699; 87%) were fewer than 5 minutes in consecutive length. Among the mean 7.7 distinct contacts ≥2 minutes with opponents each game (median = 4; IQR = 2, 8), very few were ≥5 consecutive minutes at any point (mean = 1.0; median = 0; IQR = 0, 0). Most (n = 849; 43.2%) distinct contacts were pre-game, 546 (27.8%) were during competition, and 569 (29%) were post-game. In games where cumulative interactions were analyzed, there was an average of 17.1 player/opponent interactions with cumulative exposure ≥5 minutes (median = 12; IQR = 4, 30), almost all of which occurred during competition. CONCLUSION: There is limited and short contact between and among competing players in professional American football. In the setting of infectious disease such as the COVID-19 pandemic, a robust prevention program integrating masking, distancing, hygiene, and ventilation when off-field can be created to minimize on- and off-field exposures, which effectively reduces transmission risk in outdoors and/or well-ventilated stadium settings.

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease.

OBJECTIVE: To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. METHODS: Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. RESULTS: Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. CONCLUSIONS: In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

Low incidence and transient elevation of autoantibodies post mRNA COVID-19 vaccination in inflammatory arthritis.

OBJECTIVES: Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls. METHODS: Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization. RESULTS: Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, p= 0.014). Incidence of de novo anti-cyclic citrullinated protein (CCP) seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titer, transient, and not associated with increase in IA flares. CONCLUSIONS: In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.

Effectiveness and use of reverse transcriptase polymerase chain reaction point of care testing in a large-scale COVID-19 surveillance system.

BACKGROUND: Rapid COVID-19 testing platforms can identify infected individuals at the point of care (POC), allowing immediate isolation of infected individuals and reducing the risk of transmission. While lab-based nucleic acid amplification testing (NAAT) is often considered the gold standard to detect SARS-CoV-2 in the community, results typically take 2-7 days to return, rendering POC testing a critical diagnostic tool for infection control. The National Football League (NFL) and NFL Players Association deployed a new POC testing strategy using a newly available reverse transcriptase polymerase chain reaction (RT-PCR) rapid test during the 2020 season, and evaluated diagnostic effectiveness compared to other available devices using real-world population surveillance data. METHODS: RT-PCR POC test results were compared to NAAT results from same-day samples by calculation of positive and negative concordance. Sensitivity analyses were performed for three subgroups: (1) individuals symptomatic at time of positive test; (2) individuals tested during the pilot phase of rollout; and (3) individuals tested daily. RESULTS: Among 4989 same-day POC/NAAT pairs, 4957 (99.4%) were concordant, with 93.1% positive concordance and 99.6% negative concordance. Based on adjudicated case status, the false negative rate was 0.2% and false positive rate was 2.9%. In 43 instances, the immediate turnaround of results by POC allowed isolation of infected individuals 1 day sooner than lab-based testing. Positive/negative concordance in sensitivity analyses were relatively stable. CONCLUSION: RT-PCR POC testing provided timely results that were highly concordant with lab-based NAAT in population surveillance. Expanded use of effective RT-PCR POC can enable rapid isolation of infected individuals and reduce COVID-19 infection in the community.

Population testing for COVID-19: an approach for infection prevention

BackgroundPopulation screening with highly sensitive diagnostic tools, such as nucleic acid amplification testing (NAAT), can enable early identification and isolation of cases and reduce transmission of SARS-CoV-2.ObjectiveTo describe the results of a rigorous, large-scale COVID-19 testing and monitoring program with confirmatory processes and adjudication of positive results.DesignDescriptive Epidemiology StudySetting32 U.S. National Football League (NFL) Clubs during the 2020 seasonParticipantsNFL players and staffMethodsThe NFL/NFL Players Association instituted a COVID-19 Testing and Surveillance Program for the 2020 Season, which included daily testing for players and staff, full medical follow-up and adjudication of cases. Clinical adjudication was based on subsequent daily testing, symptoms, and clinical history;persons remained in isolation during adjudication.ResultsBetween August 1 and November 14, 2020, a total of 632,370 RT-PCR tests were administered to 11,668 individuals;270 (2.4%) confirmed cases were observed. PPVs of the initial positive result ranged from 73–82% across RT-PCR platforms. Initial positive results were positive on re-processing 61–79% of the time. PPV increased when both results were positive to >95%;however, initial positives that were negative on confirmatory processing resulted in true cases a portion of the time, depending on machine and population prevalence. High Ct values (33 to 37) could indicate onset of infection. Infected individuals were identified and isolated early in infection, preventing spread.InterventionsDaily or frequent testing using three NAAT platforms, rapid point-of-care testing, and symptom monitoring.Main Outcome MeasurementsCOVID-19 infection.ConclusionRoutine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results. Confirmatory processing of initial positive values significantly improved PPV. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. Adjudication processes were able to confirm or rule out SARS-CoV-2.

Optimizing SARS-CoV-2 Surveillance in the United States: Insights From the National Football League Occupational Health Program.

BACKGROUND: Evidence to understand effective strategies for surveillance and early detection of SARS-CoV-2 is limited. OBJECTIVE: To describe the results of a rigorous, large-scale COVID-19 testing and monitoring program. DESIGN: The U.S. National Football League (NFL) and the NFL Players Association (NFLPA) instituted a large-scale COVID-19 monitoring program involving daily testing using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms (Roche cobas and Thermo Fisher QuantStudio), a transcription-mediated amplification platform (Hologic Panther), and an antigen point-of-care (aPOC) test (Quidel Sofia). SETTING: 32 NFL clubs in 24 states during the 2020 NFL season. PARTICIPANTS: NFL players and staff. MEASUREMENTS: SARS-CoV-2 test results were described in the context of medically adjudicated status. Cycle threshold (Ct) values are reported when available. RESULTS: A total of 632 370 tests administered across 11 668 persons identified 270 (2.4%) COVID-19 cases from 1 August to 14 November 2020. Positive predictive values ranged from 73.0% to 82.0% across the RT-PCR platforms. High Ct values (33 to 37) often indicated early infection. For the first positive result, the median Ct value was 32.77 (interquartile range, 30.02 to 34.72) and 22% of Ct values were above 35. Among adjudicated COVID-19 cases tested with aPOC, 42.3% had a negative result. Positive concordance between aPOC test result and adjudicated case status increased as viral load increased. LIMITATIONS: Platforms varied by laboratory, and test variability may reflect procedural differences. CONCLUSION: Routine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results, with high values often indicating early infection. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. PRIMARY FUNDING SOURCE: The NFL and the NFLPA.

Observed Versus Expected COVID-19 Infections Among National Football League Players During the 2020 Season.

BACKGROUND: The National Football League (NFL) and National Football League Players Association implemented a set of strict protocols for the 2020 season with the intent to mitigate COVID-19 risk among players and staff. In that timeframe, the league's 32 teams completed 256 regular season games and several thousand meetings and practices. In parallel, community cases of COVID-19 were highly prevalent. We assess the risk of holding a 2020 NFL season by comparing community and player COVID-19 infections. METHODS: We used county-level COVID-19 test data from each team to establish baseline distributions of infection rates expected to occur in a population similar in age and sex to NFL players. We used a binomial distribution to simulate expected infections in each community cohort and compared these findings with observed COVID-19 infections in players. RESULTS: Over a 5-month period (1 August 2020 to 2 January 2021), positive NFL player infections (n = 256) were 55.7% lower than expected when compared with simulations from NFL community cohorts. For 30 of 32 teams (94%), observed counts fell at or below expectation, including 28 teams (88%) for which rates were lower. Two teams fell above baseline expectation. CONCLUSIONS: The NFL/NFLPA protocols that governed team facilities, travel, gameday, and activities outside of the workplace were associated with lower infection rates among NFL players compared with the surrounding community. The NFL's 2020-2021 season are consistent with the hypothesis that robust testing and behavioral protocols support a safe return to sport and work.

Prevalence of Inflammatory Heart Disease Among Professional Athletes With Prior COVID-19 Infection Who Received Systematic Return-to-Play Cardiac Screening.

Importance: The major North American professional sports leagues were among the first to return to full-scale sport activity during the coronavirus disease 2019 (COVID-19) pandemic. Given the unknown incidence of adverse cardiac sequelae after COVID-19 infection in athletes, these leagues implemented a conservative return-to-play (RTP) cardiac testing program aligned with American College of Cardiology recommendations for all athletes testing positive for COVID-19. Objective: To assess the prevalence of detectable inflammatory heart disease in professional athletes with prior COVID-19 infection, using current RTP screening recommendations. Design, Setting, and Participants: This cross-sectional study reviewed RTP cardiac testing performed between May and October 2020 on professional athletes who had tested positive for COVID-19. The professional sports leagues (Major League Soccer, Major League Baseball, National Hockey League, National Football League, and the men's and women's National Basketball Association) implemented mandatory cardiac screening requirements for all players who had tested positive for COVID-19 prior to resumption of team-organized sports activities. Exposures: Troponin testing, electrocardiography (ECG), and resting echocardiography were performed after a positive COVID-19 test result. Interleague, deidentified cardiac data were pooled for collective analysis. Those with abnormal screening test results were referred for additional testing, including cardiac magnetic resonance imaging and/or stress echocardiography. Main Outcomes and Measures: The prevalence of abnormal RTP test results potentially representing COVID-19-associated cardiac injury, and results and outcomes of additional testing generated by the initial screening process. Results: The study included 789 professional athletes (mean [SD] age, 25 [3] years; 777 men [98.5%]). A total of 460 athletes (58.3%) had prior symptomatic COVID-19 illness, and 329 (41.7%) were asymptomatic or paucisymptomatic (minimally symptomatic). Testing was performed a mean (SD) of 19 (17) days (range, 3-156 days) after a positive test result. Abnormal screening results were identified in 30 athletes (3.8%; troponin, 6 athletes [0.8%]; ECG, 10 athletes [1.3%]; echocardiography, 20 athletes [2.5%]), necessitating additional testing; 5 athletes (0.6%) ultimately had cardiac magnetic resonance imaging findings suggesting inflammatory heart disease (myocarditis, 3; pericarditis, 2) that resulted in restriction from play. No adverse cardiac events occurred in athletes who underwent cardiac screening and resumed professional sport participation. Conclusions and Relevance: This study provides large-scale data assessing the prevalence of relevant COVID-19-associated cardiac pathology with implementation of current RTP screening recommendations. While long-term follow-up is ongoing, few cases of inflammatory heart disease have been detected, and a safe return to professional sports activity has thus far been achieved.

Implementation and Evolution of Mitigation Measures, Testing, and Contact Tracing in the National Football League, August 9-November 21, 2020.

The National Football League (NFL) and the NFL Players Association (NFLPA) began the 2020 football season in July, implementing extensive mitigation and surveillance measures in facilities and during travel and gameplay. Mitigation protocols* were evaluated and modified based on data from routine reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2, the virus that causes coronavirus 2019 (COVID-19); proximity tracking devices; and detailed interviews. Midseason, transmission was observed in persons who had cumulative interactions of <15 minutes' duration, leading to a revised definition of high-risk contacts that required consideration of mask use, setting and room ventilation in addition to proximity and duration of interaction. The NFL also developed an intensive protocol that imposed stricter infection prevention precautions when a case was identified at an NFL club. The intensive protocol effectively prevented the occurrence of high-risk interactions, with no high-risk contacts identified for 71% of traced cases at clubs under the intensive protocol. The incorporation of the nature and location of the interaction, including mask use, indoor versus outdoor setting, and ventilation, in addition to proximity and duration, likely improved identification of exposed persons at higher risk for SARS-CoV-2 infection. Quarantine of these persons, along with testing and intensive protocols, can reduce spread of infection.

COVID-19 in Patients With Inflammatory Arthritis: A Prospective Study on the Effects of Comorbidities and Disease-Modifying Antirheumatic Drugs on Clinical Outcomes.

OBJECTIVE: To characterize the hospitalization and death rates among patients with inflammatory arthritis (IA) affected by coronavirus disease 2019 (COVID-19) and to analyze the associations of comorbidities and immunomodulatory medications with infection outcomes. METHODS: Data on clinical and demographic features, maintenance treatment, disease course, and outcomes in individuals with IA (rheumatoid arthritis and spondyloarthritis) with symptomatic COVID-19 infection were prospectively assessed via web-based questionnaire followed by individual phone calls and electronic medical record review. Baseline characteristics and medication use were summarized for hospitalized and ambulatory patients, and outcomes with the different medication classes were compared using multivariable logistic regression. RESULTS: A total of 103 patients with IA were included in the study (80 with confirmed COVID-19 and 23 with high suspicion of COVID-19). Hospitalization was required in 26% of the participants, and 4% died. Patients who were hospitalized were significantly more likely to be older (P < 0.001) and have comorbid hypertension (P = 0.001) and chronic obstructive pulmonary disease (P = 0.02). IA patients taking oral glucocorticoids had an increased likelihood of being admitted for COVID-19 (P < 0.001), while those receiving maintenance anticytokine biologic therapies did not. CONCLUSION: Among patients with underlying IA, COVID-19 outcomes were worse in those receiving glucocorticoids but not in patients receiving maintenance anticytokine therapy. Further work is needed to understand whether immunomodulatory therapies affect COVID-19 incidence.

Return to sport for North American professional sport leagues in the context of COVID-19.

COVID-19 is a respiratory illness that can spread from person to person. A range of clinical scenarios exist, from an asymptomatic disease course to SARS and death. This document describes important considerations for 5 North American professional sports leagues (Major League Baseball, Major League Soccer, National Basketball Association, National Football League and National Hockey league) assessing when and how to resume phased operations, including practices and games. Sports should prioritise and promote the health and safety of athletes, team and operational staff, and other participants, and should not unduly increase those individuals' relative health risk while contributing to economic recovery, providing entertainment for the public and leading a responsible restoration of civic life. Because elite professional sport ordinarily is conducted in a controlled environment, professional sports leagues may be able to achieve these goals. This document is focused on professional sports leagues in North America, and although many of the statements are generalisable to professional sporting settings throughout the world, other considerations may apply to sports in other countries.