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Articles Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial Boris Revollo, Ignacio Blanco, Pablo Soler, Jessica Toro, Nuria Izquierdo-Useros, Jordi Puig, Xavier Puig, Valentí Navarro-Pérez, Cristina Casañ, Lidia Ruiz, Daniel Perez-Zsolt, Sebastià Videla, Bonaventura Clotet, Josep M Llibre Summary Background The banning of mass-gathering indoor events to prevent SARS-CoV-2 spread has had an important effect Lancet Infect Dis 2021; on local economies. Despite growing evidence on the suitability of antigen-detecting rapid diagnostic tests (Ag-RDT) 21: 1365–72 for mass screening at the event entry, this strategy has not been assessed under controlled conditions. We aimed to Published Online May 27, 2021 assess the effectiveness of a prevention strategy during a live indoor concert. https://doi.org/10.1016/ S1473-3099(21)00268-1 Methods We designed a randomised controlled open-label trial to assess the effectiveness of a comprehensive preventive See Comment page 1334 intervention for a mass-gathering indoor event (a live concert) based on systematic same-day screening of attendees For the Spanish translation of the with Ag-RDTs, use of facial masks, and adequate air ventilation. The event took place in the Sala Apolo, Barcelona, abstract see Online for Spain. Adults aged 18–59 years with a negative result in an Ag-RDT from a nasopharyngeal swab collected immediately appendix 1 before entering the event were randomised 1:1 (block randomisation stratified by age and gender) to either attend the Division of Infectious diseases indoor event for 5 hours or go home. Nasopharyngeal specimens used for Ag-RDT screening were analysed by real-time and Foundation for Fighting AIDS, Infectious Diseases and reverse-transcriptase PCR (RT-PCR) and cell culture (Vero E6 cells). 8 days after the event, a nasopharyngeal swab was Promoting Health and Science collected and analysed by Ag-RDT, RT-PCR, and a transcription-mediated amplification test (TMA). The primary (B Revollo MD, J Toro MBiolSci, outcome was the difference in incidence of RT-PCR-confirmed SARS-CoV-2 infection at 8 days between the control and J Puig APRN, S Videla MD, the intervention groups, assessed in all participants who were randomly assigned, attended the event, and had a valid B Clotet MD, J M Llibre MD) and IrsiCaixa AIDS result for the SARS-CoV-2 test done at follow-up. The trial is registered at ClinicalTrials.gov, NCT04668625. Research Institute (N Izquierdo-Useros PhD, Findings Participant enrollment took place during the morning of the day of the concert, Dec 12, 2020. Of the 1140 people L Ruiz PhD, D Perez-Zsolt PhD, who responded to the call and were deemed eligible, 1047 were randomly assigned to either enter the music event B Clotet) University Hospital Germans Trias i Pujol, (experimental group) or continue with normal life (control group). Of the 523 randomly assigned to the experimental Badalona, Spain; group, 465 were included in the analysis of the primary outcome (51 did not enter the event and eight did not take part Metropolitana Nord in the follow-up assessment), and of the 524 randomly assigned to the control group, 495 were included in the final Laboratory, Institut Català de la Salut, Badalona, Spain analysis (29 did not take part in the follow-up). At baseline, 15 (3%) of 495 individuals in the control group and (I Blanco MD, C Casañ PharmG); 13 (3%) of 465 in the experimental group tested positive on TMA despite a negative Ag-RDT result. The RT-PCR test was Primavera Sound Group, positive in one case in each group and cell viral culture was negative in all cases. 8 days after the event, two (<1%) Barcelona, Spain (P Soler LLB); individuals in the control arm had a positive Ag-RDT and PCR result, whereas no Ag-RDT nor RT-PCR positive results Germans Trias i Pujol Research Institute (IGTP), Can Ruti were found in the intervention arm. The Bayesian estimate for the incidence between the experimental and control Campus, Badalona, Spain groups was –0·15% (95% CI –0·72 to 0·44). (N Izquierdo-Useros, D Perez-Zsolt); Department of Interpretation Our study provides preliminary evidence on the safety of indoor mass-gathering events during a Statistics and Operations Research, Universitat Politècnica COVID-19 outbreak under a comprehensive preventive intervention. The data could help restart cultural activities de Catalunya-BarcelonaTech, halted during COVID-19, which might have important sociocultural and economic implications. Barcelona, Spain (X Puig PhD); Clinical Research Unit, Institut Funding Primavera Sound Group and the #YoMeCorono Initiative. Català d’Oncologia (V Navarro-Pérez MSc) and Clinical Research Support Unit, Copyright © 2021 Elsevier Ltd. All rights reserved. Clinical Pharmacology Department, Bellvitge Introduction Of all mass-gathering events banned during the University Hospital, University of Barcelona (S Videla), Bellvitge Mass-gathering events are associated with a high risk of COVID-19 pandemic, the closure of concert halls has had Biomedical Research Institute spreading SARS-CoV-2.1,2 Cultural activities such as a remarkable impact on local economies. In 2019, music (IDIBELL), L’Hospitalet de sporting events, indoor gatherings, plays, or concerts festivals had an estimated revenue of more than Llobregat, Barcelona, Spain; have been identified as the most high-risk venues for €5·5 billion in Spain and €2·5 billion in Catalonia. The Universitat de Vic-Universitat Central de Catalunya (UVIC- SARS-CoV-2 transmission.3 Health-care authorities have cancellation and deferment of these events in 2020 UCC), Vic, Spain (B Clotet); correspondingly reduced the capacity of the venues to resulted in substantial economic losses, and restrictions Department of Medicine, prevent close contact between unknown attendees or on their celebration or capacity remain in force in 2021. Universitat Autònoma de have cancelled all events, despite the lack of scientific One of the key factors that challenges the control of Barcelona, Barcelona, Spain (B Clotet) evidence for such increased risk. SARS-CoV-2 transmission in mass-gathering events is the www.thelancet.com/infection Vol 21 October 2021 1365 Articles Correspondence to: Dr Josep M Llibre, Division of Research in context Infectious diseases and Foundation for Fighting AIDS, Evidence before this study including same-day SARS-CoV-2 screening with antigen-detecting Infectious Diseases and On March 30, 2021, we searched PubMed for articles published rapid diagnostic tests (Ag-RDTs), compulsory N95 face mask Promoting Health and Science, in English using the terms “mass-gathering event” and wearing, and optimised air ventilation. Participants could sing and University Hospital Germans Trias i Pujol, “COVID-19”. The search returned 31 results, most of them dance in the concert hall room, and no physical distancing was 08916 Badalona, Spain corresponding to articles that either described mitigation plans recommended. None of the 465 participants became infected, jmllibre@flsida.org or reported retrospective analyses of SARS-CoV-2 spread during compared with two out of 495 in the control arm. For more on the #YoMeCorono mass-gathering events. None of the articles found reported Initiative see https://www. Implications of all the available evidence the results of a controlled experiment in which preventive yomecorono.com/ Our study provides preliminary evidence on the effectiveness of measures were used to create a safe environment during a same-day point-of-care screening with Ag-RDT, combined with mass-gathering event. face mask-wearing and active air ventilation, to create safe Added value of this study indoor environments with no need for physical distancing To our knowledge, this is the first randomised clinical trial that measures. Future studies with a larger capacity of attendees assesses the risk of COVID-19 transmission in an indoor mass- and assistants, and done during periods of increased gathering live concert done under comprehensive safety measures, transmission of COVID-19 are warranted. difficulty in identifying individuals who can transmit the to prevent SARS-CoV-2 spread during an indoor live See Online for appendix 2 virus because they are infected with a high viral load, concert (appendix 2 p 2). The study took place in the particularly asymptomatic or pre-symptomatic people with Sala Apolo, a concert venue in Barcelona, Spain. Study a high viral load.4 SARS-CoV-2 transmissibility begins 2 participants were recruited from a list of subscribers to to 3 days before symptom onset, and nearly half of the news related to live music events; a call for enrolling transmissions occur from asymptomatic individuals.5 in the study was done through non-official media, The long turnaround time required for nucleic- including WhatsApp, Telegram, and email. Eligible acid amplification tests (NAATs)—including the gold participants were adults aged 18–59 years with a negative standard real-time reverse transcriptase-PCR (RT-PCR)— result in an Ag-RDT from a nasopharyngeal swab for identifying SARS-CoV-2 in respiratory specimens collected in the morning of the day of the event (from creates difficulties in implementing mass testing about 12 h before the event began). Participants with strategies on the same day of the event. Alternatively, known COVID-19 diagnosis within the 14 days before antigen-detecting rapid diagnostic tests (Ag-RDTs) have the event, relevant comorbidities (including hyper­ been proposed as suitable tools for point-of-care screening tension, diabetes, or any type of cancer), or living with of individuals infected with SARS-CoV-2. The main older people were excluded (appendix 2 p 3). The study advantages of Ag-RDTs include low price, absence of need protocol was approved by the Ethics and Clinical for high-tech laboratory referral, and a short turnaround Research Committee of the Hospital Universitari time to provide a result. Despite the overall lower Germans Trias in Badalona, Spain. All participants sensitivity of Ag-RDTs than NAAT, a growing body of signed informed consent electronically, including the evidence indicates that they are suitable for identifying acceptance of not entering the event if allocated in individuals who could potentially transmit the virus.6–8 the control arm. The study was done according to Current evidence on Ag-RDT performance suggests that a the Declaration of Helsinki and local legislation. point-of-care screening of contagious individuals, together with containment measures, such as the use of adequate Randomisation and masking facial masks and optimised ventilation, can create safe Study participants with a negative result from environments for mass-gathering events with low risk of Ag-RDT nasopharyngeal swab testing were randomly SARS-CoV-2 spread. However, this approach has not been assigned (1:1) to either enter the indoor live event tested under controlled conditions. We did a randomised (experimental group) or not enter the event and return to controlled trial to assess the effectiveness of a prevention normal life (control group). The computer-generated strategy during a live indoor concert, under the hypothesis block randomisation (REDCap module) was stratified that same-day point-of-care screening of infected individuals by age, gender, and previous COVID-19 episode reported and regular preventive measures would prevent an increased in the questionnaire. Participants allocated to the risk of SARS-CoV-2 transmission during the event. experimental group also returned to normal life after the event. By the time of study conduct, mobility was Methods constrained to the municipality, and indoor meetings of Study design and participants more than six people were banned. Face mask use was We did an open-label, randomised (1:1) clinical trial to mandatory indoors and outdoors, except in the outdoor assess the effectiveness of a comprehensive intervention controlled smoking area. 1366 www.thelancet.com/infection Vol 21 October 2021 Articles The team of nurses that did the mass screening also did permitted. A smoking area was set up outdoors; the area the computer-generated block randomisation using the had 20 people capacity and strict control of crowding and REDCap module and sent the results of the allocation physical distancing. Masks could be removed in through the app installed on all participant smartphones. the outdoor smoking area due to physical distancing They had no further role in the trial. controlled by a security crew. This was an open-label study in which both participants Drinks, including alcoholic beverages, were served and investigators knew to which groups participants had only in the bar zone, located in an extra room with a been randomly assigned. capacity for 1600 people. Participants were asked to remove their face mask only when drinking. Movement Procedures within the venue was signposted, some sites of the venue Before starting the music event, the health-care staff were closed, and the direction of movement was (45 nurses and one physician) collected naso­pharyngeal controlled by the security crew that controlled any queue swabs from all eligible participants in a screening structure formation. Securities personnel oversaw all movements set up outdoors in front of the concert venue, with and acted, if necessary, to prevent queues in and around 24 awnings. The mass screening started at 8:00 am and the venue foyer and toilets. Hydroalcoholic hand sanitizer finished at 3:30 pm on the day the music event took place gel was provided at multiple points in the venue. (Dec 12, 2020). The same nasopharyngeal specimen was The temperature of the dancing room and bar were used for in situ Ag-RDT (Panbio COVID-19 Ag Rapid Test, maintained between 19·3 and 20·4 ºC during the event Abbott) and a transcription-mediated amplification test to facilitate wearing the mask and coats (the cloakroom (TMA, Procleix Panther, Grifols). The result was reported was closed to avoid queues in front of it). Average carbon after 15 min through the app installed in the smartphone dioxide (CO2) measurements before starting the event of every participant. This immediate reporting of results were 440 ppm in the dancing hall and 417 ppm in the bar allowed randomisation of individuals who could attend the room, both similar to those typically obtained in open air live music event in the afternoon. The TMA result was in the city. Public health safety guidance in force by the reported 24–48 h after ending the event. All TMA-positive time of the event recommended not exceeding samples were re-tested by RT-PCR. The day after releasing 800–1000 ppm during the event.11 the result, a study physician contacted all individuals with The total surface area of the venue was 1024 m², which a positive TMA result by phone and screened their medical included 228 m² for the dancing hall, 381 m² for the bar records to identify the exact date of a previous positive hall, and 157 m² in the lobby. There were no exterior SARS-CoV-2 diagnostic test. All swabs with positive TMA windows in the two respective halls; however, all access results were assessed for viral isolation on cell culture. and exit doors remained open during the event, allowing All study participants were visited 8 days after the event additional fresh air from the inner courtyard. for nasopharyngeal swab collection and TMA test The event, held in the Sala Apolo (Barcelona, Spain) on (follow-up day 8 test). According to current evidence December 12, 2020, lasted for 5 h and included on SARS-CoV-2 kinetics, an assessment done on day 8 four performances: two DJ sessions and two live music maximizes the likelihood of capturing infections caused acts. Besides the study participants and artists, 58 staff during the live event.5,9,10 members (organizers, security, sound, light technicians, All participants installed two smartphone applications and bartenders) were inside the venue during the (apps). The Radar Covid application (a contact tracing event. All of them were tested for SARS-CoV-2 using app) was intended to capture close contacts of participants Ag-RDT at the same time points as the study participants. potentially infected during the concert. The Test-Wallet Nasopharyngeal specimens were collected with flocked app was used to confidentially report the study test swabs in a viral universal transport medium (Deltalab SL, results (ie, Ag-RDT, TMA, and PCR) and fill in a health Barcelona, Spain). Samples were received at the labo­ questionnaire before and 10 days after the event, and a ratory and were processed immediately, inactivated, satisfaction questionnaire for those attending the concert and analysed by TMA. All TMA-positive results were (appendix 2 pp 4–5). Data generated by the Test-Wallet confirmed by RT-PCR assay to determine the cycle app were encrypted using SHA-1 encryption and with threshold (Ct) values (AllplexTM SARS-CoV-2, Seegene) 256-bit SSL security certificate. All SARS-CoV-2 positive using the software designed by the company. Leftover results were reported into the public health electronic positives samples were conserved at –80°C. system and triggered quarantining measures and contact Nasopharyngeal specimens with positive SARS-CoV-2 tracing studies. TMA results that had tested negative with Ag-RDT were Forehead body temperature was monitored at the analysed for viral isolation on cell culture. Vero E6 cells entrance of the screening site and concert venue, where (ATCC CRL-1586) were cultured in Dulbecco’s modified all participants received an N95 mask. Mask wearing Eagle medium (DMEM) supplemented with 10% heat- was mandatory during the entire event. No physical inactivated fetal bovine serum (FBS), 100 U/mL penicillin, distancing was required in the concert room (with a and 100 µg/mL streptomycin (Invitrogen). Two individuals capacity of 900 people); singing and dancing were with negative SARS-CoV-2 RT-PCR, and two viral stocks www.thelancet.com/infection Vol 21 October 2021 1367 Articles For more on R software see previously isolated were cultured in triplicates as negative The analyses were done with R and the Bayesian https://www.gbif.org/ controls as previously described.12 DMEM supplemented software JAGS.16 The trial is registered at ClinicalTrials. tool/81287/r-a-language-and- environment-for-statistical- with FBS and penicillin/streptomycin were supplied to gov, NCT04668625. computing cells and inspected every 2 days for cytopathic effects. On day 7, cell supernatants were assayed with a high- Role of the funding source sensitivity quantitative ELISA for SARS-CoV-2 nucleo­ The study sponsor had no role in study design, data capsid protein (ImmunoDiagnostics). collection, data analysis, data interpretation, or writing of the report. Outcomes The primary outcome was to evaluate the risk of Results transmission of SARS-CoV-2 in a mass-gathering indoor Participant enrolment and the live music event took music event with the implementation of safety strategies place on Dec 12, 2020. A total of 1140 participants to reduce the spread of COVID-19. The primary efficacy responded to the call released through social networks, endpoint was the difference in the incidence of RT-PCR- were deemed eligible, and were invited to participate in confirmed SARS-CoV-2 infection at 8 days between the study. Of these, 93 individuals did not attend, and the control and the intervention groups. The primary 1047 individuals turned out for the event and were outcome was assessed in the full analysis set, which screened for SARS-CoV-2 infection with Ag-RDT via a included all participants who were randomly assigned, nasopharyngeal swab. All participants tested negative attended the event (in the experimental arm), and had a and were randomly assigned to either of the two trial valid result for the SARS-CoV-2 test done on day 8. arms (the experimental group to attend the music event, or the control group to not attend the event and continue Statistical analysis with daily life). In the experimental group, 51 participants We used a Bayesian beta-binomial model to analyse the did not enter the live music event, and seven participants number of infected cases in each group. This approach did not have a follow-up assessment, resulting in allows previous information to be included, which is 465 participants with data assessed for the primary useful when estimating the probability of rare events.13,14 outcome. In the control group, 29 participants did not The 7-day cumulative incidence observed in the city of have a follow-up assessment, resulting in 495 participants Barcelona when the follow-up RT-PCR was done on day 8 with data assessed for the primary outcome (figure). after the live music event was about 1·3 cases per Participants included in the full analysis set had a 1000 people, according to official data.11 Considering this mean age of 33·6 years (SD 8·6); 783 (82%) were men incidence, we estimated the ideal number of participants and 177 (18%) were women. Individuals in the to be 1000 per study arm. However, this value under­ intervention group spent a median of 2 h and 40 min estimates the true rates due to the difficulty in recording inside the concert. asymptomatic cases. The study population had some Of the 960 participants included in the full analysis set, exclusion and inclusion criteria that could influence this all tested Ag-RDT negative in the baseline screening, and value. For the control group, the prior distribution chosen 28 (3%) had a positive TMA result (13 in the experimental was a Beta (1·1, 400), with a median of 0·002, and the group and 15 in the control arm). Of these 28, two (one in probability of values greater than 0·01 is approximately each arm) had a positive RT-PCR result (Ct 37 for both; 2%. Uncertainty about the probability of infection among table). The 14-day attack rate in Catalonia in the same the experimental group was higher, and a Beta (1, 28·4) calendar week (Dec 7–13, 2020) and population group was chosen, with a probability of obtaining values greater was 220·7 cases per 100 000 inhabitants.11 According to than 0·1 around 5% as a prior distribution. For each the interview by a physician and medical records review, group, the posterior median and the highest posterior all participants with positive TMA results had been density interval were calculated. Additionally, to compare previously diagnosed with COVID-19 within a median of the probabilities of infection between groups, the 50 days (IQR 44–77) before the event. None of the difference in their probabilities and its credible interval 28 specimens with a positive TMA result showed a (CI) were calculated. cytopathic effect on cell cultures, as measured with a The negative predictive value of the Ag-RDT was quantitative ELISA 7 days post-inoculation. Conversely, estimated, taking as reference tests the RT-PCR and control positive cultures showed evident cytopathic cell culture and using the Bayesian Markov Chain effect, and viral particles could be detected by ELISA. Monte Carlo (MCMC) method as proposed by Gelman None of the 465 participants in the experimental group and colleagues.15 For the prevalence, a Beta (1·1, 400) was became infected by SARS-CoV-2 (observed incidence 0%; chosen again as a prior distribution, and the sensitivity estimated incidence 0·14%, 95% CI 0–0·61) versus and specificity are given with a non-informative two of 495 controls (0·31%, 0·04–0·73), as assessed by a Beta (1, 1) priors. The median and the highest posterior positive RT-PCR test on day 8. The two participants in the density CI were calculated for the negative predictive control group with SARS-CoV-2 infection had positive value. Ag-RDT and RT-PCR (Ct values 26·3 and 28·3) results in 1368 www.thelancet.com/infection Vol 21 October 2021 Articles the follow-up assessment on day 8. Both had mild clinical disease and were reported to the health-care system. An 1140 people assessed for eligibility and deemed eligible for inclusion epidemiological questionnaire and contact tracing were done. One of them had already been diagnosed 4 days after the randomisation had occurred. Except for the 93 people did not attend on specified date of event two individuals with positive RT-PCR and Ag-RDT tests, all individuals with a positive TMA result on day 8 had a 1047 participants were randomised history of a positive nasopharyngeal specimen (assessed either with TMA or RT-PCR) within the 52 days (IQR 45–81) before the event. The incidence difference, estimated using a Bayesian approach, did not reveal 524 randomly assigned to control group 523 randomly assigned to experimental group to attend music event significant differences in incidence between the two groups. The Bayesian estimate for the incidence between the experimental and control groups was 51 did not enter event 35 with companions randomly assigned –0·15% (95% CI –0·72 to 0·44). to control group The negative predictive value of the Ag-RDT screening 16 received a delayed communication of in this cohort of asymptomatic individuals was 99·9% randomisation result due to temporary interruption of the (95% CI 99·5–100) for a positive RT-PCR, and 99·8% informatic system (99·3–100) for a positive viral culture. The air concentration of CO2 did not exceed the 472 attended music event recommended threshold of 800 ppm at any time point during the event.17 The number of complete air exchanges per h in the two rooms ranged from 11 to 13. 29 did not take part in follow-up assessment 8 did not take part in follow-up assessment The median score of the questionnaire assessing satisfaction and enjoyment during the event, rated on a 495 included in analysis of primary outcome 465 included in analysis of primary outcome ten-point scale, was 8·63 (IQR 6–10). Most event attendees felt they could behave normally and Figure: Trial profile non-constrained despite the safety measures (median score 8·08, IQR 5–10). They expressed their willingness to attend another activity with the same safety protocol Control group Experimental group (median score 9·29, IQR 9–10). There were neither (n=495) (n=465) disturbances nor interventions of security personnel Baseline screening aside from reminders of wearing the face mask during the event. Ag-RDT positive 0 0 The staff crew inside the venue included 58 people TMA positive* 15 (3·0%) 13 (3%) (organizers, security, sound and light technicians, and Cell culture positive 0 0 bartenders). All of them had negative Ag-RDT and RT-PCR positive 1 (<1%) 1 (<1%) RT-PCR results at baseline and the follow-up visit on Ct value 37 37 day 8. Follow-up assessment Ag-RDT positive 2 (0·4%) 0 Discussion TMA positive† 15 (3·0%) 12 (3%) To our knowledge, this is the first randomised clinical TMA positive at baseline 4 3 trial that assesses the risk of COVID-19 transmission in TMA negative at baseline 11 9 an indoor mass-gathering live concert done under RT-PCR positive 2 (0·4%) 0 comprehensive safety measures, including same-day Ct value 26·3; 28·3 NA SARS-CoV-2 screening with Ag-RDTs, compulsory Infected with SARS-CoV-2 2 (0·4%) 0 N95 face mask wearing, and optimised air ventilation. Ag-RDT=antigen-detecting rapid diagnostic tests. TMA=transcription-mediated Participants were encouraged to sing and dance in the amplification test. RT-PCR=real-time reverse transcriptase-polymerase chain reaction. concert hall room, and no physical distancing was Ct=cycle threshold. NA=not applicable. *Three TMA results in the control group were inconclusive. †One TMA result in the experimental group was inconclusive. recommended. None of the 465 participants became infected, compared with two of 495 in the control arm. Table: Virological assessment results for SARS-CoV-2 at baseline and High SARS-CoV-2 attack rates (53% of confirmed day 8 after the event cases) following exposure at events involving people singing (eg, a choir practice) without face masks have itself, and has subsequently been confirmed in other been previously documented.18 Airborne transmission indoor events by high aerosol exposure indexes.19 These was considered to be facilitated by close proximity (within superspreading events emphasised the importance of 1·8 m) during practice and increased by the act of singing physical distancing, including avoiding large indoor www.thelancet.com/infection Vol 21 October 2021 1369 Articles gatherings, and played a role in issuing restrictions higher than the Ct cutoff associated with transmission against indoor cultural activities. Our study shows that risk. All had been diagnosed with COVID-19 a median of the implemented safety measures can effectively 50 days before the event and therefore had no potential for diminish this risk. viral transmission (immunosuppressed participants were A key intervention to remove physical distancing in this excluded). Unexpectedly, some TMA tests in our partici­ study was the screening of SARS-CoV-2 infection with pants were positive in those with previously confirmed Ag-RDTs immediately before entering the event. Despite COVID-19 up to 5·5 months before the event. Notably, their lower overall sensitivity than RT-PCR, Ag-RDTs have none of the TMA-positive samples from participants with proven the ability to detect SARS-CoV-2 infection in a previous SARS-CoV-2 infection were associated with respiratory specimens with Ct in RT-PCR below 25 positive cell culture. Taken together, our findings suggest (sensitivity of 100%) and below 30 (sensitivity 98·6%), that high-sensitive techniques such as TMA are not regardless of age and the presence of symptoms.6,20 suitable as screening tools for creating safe environments Although the sensitivity of these tests decreases at Ct in indoor events because they would exclude people that beyond this threshold, a growing body of evidence have had COVID-19 in previous weeks or months, and indicates that respiratory specimens with Ct values of those who have recovered and no longer have the potential more than 30 have a diminished infection capacity.9,10,21,22 to transmit the virus. Therefore, the systematic screening of potential attendees Aside from baseline screening, our intervention to an indoor event is an excellent tool for ruling out included other containment measures that might have SARS-CoV-2 infectious transmitters. In our real-life contributed to the safety of the event. N95 mask-wearing experience with the screening of asymptomatic indi­ was mandatory during the event, except when drinking viduals, Ag-RDTs had a negative predictive value of 99·9% (alcoholic beverages were allowed) or smoking. The lack for RT-PCR and 99·8% for viral culture, in agreement of facial mask-wearing during indoor activities without with previous reports.23 physical distancing measures had been pointed out as a The use of Ag-RDTs for systematic screening purposes high-risk scenario for superspreading events.18 in mass gathering events has multiple advantages Other measures that potentially contributed to creating a over NAATs, including the lack of need for laboratory safe environment included limited movement of referrals and short turnaround times to report the result. participants inside the venue, avoidance of queues in However, the low analytical sensitivity of these tests and restrooms and at entry or exit of the concert, the presence the dynamics of SARS-CoV-2 infection suggest that a of dispensers of hydroalcoholic sanitizer gel, and controlled negative result with Ag-RDT can only rule out the environment conditions. Limited air exchange in closed potential for transmitting the virus within the few hours spaces is associated with an increased risk of SARS-CoV-2 following the test.6,7 Another consideration regarding this transmission.26 Multiple infection events that prompted screening strategy is the controversy on whether tests the banning of massive gatherings27 have been associated done by non-trained people (including self-testing) with inadequate ventilation.28 In our study, all air flows and achieve the same accuracy as that reported for tests done room ventilation were optimised in the indoor rooms, and by health-care workers.8 air exchange was monitored during the entire event. The high sensitivity of NAAT is associated with the CO2 measurements were maintained below or around drawback of yielding positive results in respiratory 800 ppm in the two crowded zones (dancing and bar specimens from individuals with past infection, albeit areas). Notably, after the event, local authorities intensified doubtful or no infectious capacity.10 This is particularly the air quality recommen­ dations beyond European pervasive in TMA-based tests, with a limit of detection guidelines;17 according to the updated thresholds, air as low as 60 copies per mL (by contrast with approxi­ quality during our event would have been categorised as mately 5000 copies per mL for RT-PCR) that allows median or good, but not optimal. Therefore, in future identifying SARS-CoV-2 RNA remains some months mass-gathering indoor events, air ventilation would be set after the COVID-19 episode.24 Despite the fact that to maintain a maximum of 500 ppm (good quality) or infectious viruses have not been recovered beyond 350 ppm (optimum quality). 12 days in immuno­ competent individuals, intestinal The deployment of screening strategies such as the one biopsies obtained from asymptomatic individuals used in our experiment is challenged by the need to test 4 months after the onset of COVID-19 have revealed thousands of people within a few hours before the mass persistence of SARS-CoV-2 nucleic acids by in situ gathering event.26 Therefore, organisational difficulties hybridisation of half of the samples.25 and costs should be considered. Because of these In line with these findings, various individuals (3% in challenges, mHealth solutions such as the Test-Wallet our study) with a history of COVID-19 diagnosis (median smartphone app, designed to promptly manage Ag-RDT of 50 days before the event) tested positive for TMA in our results while maintaining users’ privacy, can substantially study despite a negative result in the Ag-RDT screening. help to manage screening procedures and result delivery. Only 7% of those with positive TMA results had a positive When balancing the costs and benefits of the intervention, RT-PCR test, all with Ct values of 37 or more, which was the public health implications of identifying and isolating 1370 www.thelancet.com/infection Vol 21 October 2021 Articles asymptomatic SARS-CoV-2-infected individuals of age might allow easing some of the additional preventive groups that often remain undetected should also be measures, particularly in indoor events with preassigned considered. seats (ie, theatres), associated with lower transmission The SARS-CoV-2 transmission results from our risk. Besides the aforementioned limitations, our study must be placed in the context of the existing findings must be placed in the context of the evolving epidemiological situation at that time. The fourth nature of the COVID-19 pandemic. Widespread vacci­ round of the national longitudinal sero-epidemiological nation campaigns, changes in local incidence, and ENE-COVID study was done in Spain during the emergence of COVID-19 variants with higher November 16–29, 2020 (the closest date to the concert) with transmissibility might shift the expected results of the 51 409 participants. According to the IgG results, the intervention. Therefore, future trials done in different accumulative prevalence of participants with a positive scenarios of the COVID-19 pandemic should confirm result in the area of Barcelona was 12·4%, with 9·8% having their safety and characterise the contribution of each of a positive result during the fourth round. The day before the preventive measures undertaken within the the indoor event, 256 new COVID-19 cases were reported comprehensive intervention. Our findings pave the way in the city of Barcelona (1·6 million people); the 14-day attack to reactivate cultural activities halted during COVID-19, rate in Catalonia was 220·7 cases per 100 000 inhabitants, which could have important sociocultural and economic and the number of active cases (during the past 14 days) implications. was 16 696, with 309 388 cumulative cases and an effective Contributors growth potential (EGP) of 210 (of concern when >150).11 BR, SV, BC, and JML conceived the project and designed the study. The week after the concert (before the follow-up RT-PCR at PS recruited participants and organised the venue framework. JP screened the virological tests of all participants. JT managed the day 8), EGP increased to 371. Because of the low number of database. XP and VN-P did the statistical analyses. IB and CC did the COVID-19 cases expected given the epidemiological laboratory analyses on clinical samples. NI-U and DP-Z did the scenario, we considered the Bayesian estimate of the SARS-CoV-2 cell cultures. JT, JP, BR, and JML accessed and verified the infection rate as an appropriate approach to the primary data. BR and JML wrote the paper. All authors had the opportunity to discuss the results and comment on the manuscript. All authors had full endpoint. access to all the data in the study and had final responsibility for the Our study has some limitations. First, participants decision to submit for publication. could have modified their behaviour during the event Declaration of interests due to their awareness of being observed, having signed PS is an employee and stockholder of Primavera Sound, sponsor of the an informed consent, and participating in a clinical study. All other authors declare no competing interests. trial. This phenomenon, known as the Hawthorne effect, Data sharing is intrinsic to clinical trials and can limit the applicability The complete de-identified participant data set will be available upon of the results to a real-life scenario. However, in the request to jtoro@flsida.org for researchers whose proposed use of the data has been approved, for any purpose. Data will be available with post-event questionnaire, all participants stated normal publication. If needed, requests will require the ethics committee approval behaviour during the event, without feeling under the of the University Hospital Germans Trias i Pujol in Badalona (Spain). scrutiny of security controls. Second, the planned Anonymised data are fully available on reasonable request from the corresponding author after approval by the hospital ethics committee. number of participants (1000 per study arm) had to be halved due to restrictions issued by local health-care Acknowledgments We thank Cristian Tebé for his collaboration in the statistical analyses, authorities. Our results encourage future studies Gerard Carot-Sans for providing medical writing support, and Jordana with venues at an estimated full capacity. Finally, Muñoz-Basagoti for her help with SARS-CoV-2 viral cultures. We thank all 16 participants did not attend the event because the study participants and the nursing team that did the screening before and result of the randomisation was communicated too after the concert, particularly Aroa Nieto and Patricia Cobarsi. We also thank Last Tour, Live Nation, Catalan Institut of Cultural Companies, close to the event and at that time they had already Department of Culture (Generalitat de Catalunya), Barcelona Institut of returned home. This delay was not due to the pace in Culture and Barcelona Municipal Services Barcelona Town/City Council, the performance of screening tests but to a computer Sala Apolo, Brunch, Universal Music Group, Global Talent services, centre failure involving the block randomisation. Sony Music, Cruïlla, Razzmatazz, Barcelona Beach Festival, Jagermeister, Elrow Family, Monegros Desert Festival, Sonorama Producciones SL, Therefore, it should not effect Ag-RDT mass screening The Wild Seeds, Sociedad General de Autores y Editores, Vampire, in future events. Sala Zero, Ticketmaster, RECUP, Taller de Musics, Madness Live!, and In summary, our study provides the first approach Fundació Banc Sabadell. to evidence building on the safety of indoor mass References gathering events done during the COVID-19 outbreak 1 Althouse BM, Wenger EA, Miller JC, et al. Superspreading events in the transmission dynamics of SARS-CoV-2: opportunities for without physical distancing measures and based on a interventions and control. PLoS Biol 2020; 18: 1–13. comprehensive preventive intervention, including same- 2 Adam DC, Wu P, Wong JY, et al. Clustering and superspreading day screening with Ag-RDT, compulsory facial mask- potential of SARS-CoV-2 infections in Hong Kong. Nat Med 2020; 26: 1714–19. wearing, and adequate ventilation. Ag-RDT screening 3 Centers for Disease Control. Events and gatherings: readiness and was effective in identifying infectious individuals com­ planning tool. 2021. https://www.cdc.gov/coronavirus/2019-ncov/ pared with RT-PCR and TMA. The results regarding community/large-events/considerations-for-events-gatherings.html virological assessment suggest that a baseline screening (accessed Feb 2,2021). www.thelancet.com/infection Vol 21 October 2021 1371 Articles 4 Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV 18 Hamner L, Dubbel P, Capron I, et al. High SARS-CoV-2 attack rate infection from an asymptomatic contact in Germany. N Engl J Med following exposure at a choir practice—Skagit County, Washington, 2020; 382: 970–71. March 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 606–10. 5 He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding 19 Liu H, He S, Shen L, Hong J. Simulation-based study of COVID-19 and transmissibility of COVID-19. Nat Med 2020; 26: 672–75. outbreak associated with air-conditioning in a restaurant. 6 Alemany A, Baro B, Ouchi D, et al. Analytical and clinical Phys Fluids 2021; 33: 023301. performance of the panbio COVID-19 antigen-detecting rapid 20 Pilarowski G, Marquez C, Rubio L, et al. Field performance and diagnostic test. J Infect 2021; 82: 186–230. public health response using the BinaxNOW TM Rapid 7 Mina MJ, Parker R, Larremore DB. Rethinking Covid-19 test SARS-CoV-2 antigen detection assay during community-based sensitivity—a strategy for containment. N Engl J Med 2020; testing. Clin Infect Dis 2020; published online Dec 26. 383: e120. https://doi.org/10.1093/cid/ciaa1890. 8 Mina MJ, Andersen KG. COVID-19 testing: one size does not fit all. 21 Marks M, Millat P, Ouchi D, et al. Transmission of COVID-19 in Science 2021; 371: 126–27. 282 clusters in Catalonia, Spain: a cohort study. Lancet Infect Dis 9 Gniazdowski V, Morris CP, Wohl S, et al. Repeat COVID-19 2021; 21: 629–36. molecular testing: correlation of SARS-CoV-2 culture with 22 Guglielmi BG. Rapid coronavirus tests: a guide for the perplexed. molecular assays and cycle thresholds. Clin Infect Dis 2021; Nature 2021; 590: 202–05. published online Oct27. https://doi.org/10.1093/cid/ciaa1616. 23 Pekosz A, Parvu V, Li M, et al. Antigen-based testing but not real- 10 Kim M-C, Cui C, Shin K-R, et al. Duration of culturable SARS-CoV-2 time polymerase chain reaction correlates with severe acute in hospitalized patients with Covid-19. N Engl J Med 2021; 384: 671–73. respiratory syndrome coronavirus 2 viral culture. Clin Infect Dis 11 Català M, Cardona P-J, Prats C, et al. Daily report 11–12–2020. 2021; published online Jan 20. DOI: https://doi.org/10.1093/cid/ Analysis and prediction of COVID-19 for EU-EFTA-UK and other ciaa1706. countries. 2020. https://upcommons.upc.edu/handle/2117/334310 24 Gorzalski AJ, Tian H, Laverdure C, et al. High-throughput (accessed May 7, 2021). transcription-mediated amplification on the hologic panther is a 12 Rodon J, Muñoz-Basagoiti J, Perez-Zsolt D, et al. Identification of highly sensitive method of detection for SARS-CoV-2. J Clin Virol plitidepsin as potent inhibitor 1 of SARS-CoV-2-induced 2020; 129: 104501. 2 cytopathic effect after a drug repurposing screen. Front Pharmacol 25 Gaebler C, Wang Z, Lorenzi JCC, et al. Evolution of antibody 2021; 12: 646676. immunity to SARS-CoV-2. Nature 2021. 591: 639–44. 13 Winkler RL, Smith JE, Fryback DG. The role of informative priors 26 Moritz S, Gottschick C, Horn J, et al. The risk of indoor sports and in zero-numerator problems. Am Stat 2002; 56: 1–4. culture events for the transmission of COVID-19 (restart-19). 14 Tuyl F, Gerlach R, Mengersen K. A comparison of Bayes–Laplace, medRxiv 2020; published online Nov 3. https://doi. Jeffreys, and other priors. Am Stat 2008; 62: 40–44. org/10.1101/2020.10.28.20221580 (preprint). 15 Gelman A, Carpenter B. Bayesian analysis of tests with unknown 27 Koizumi N, Siddique AB, Andalibi A. Assessment of SARS-CoV-2 specificity and sensitivity. J R Stat Soc Ser C 2020; 69: 1269–83. transmission among attendees of live concert events in Japan using contact-tracing data. J Travel Med 2020; 27: 1–3. 16 Plummer M. JAGS version 4.0.0 user manual. 2015. http://www. uvm.edu/~bbeckage/Teaching/PBIO_294/Manuals/manual.jags. 28 Sugano N, Ando W, Fukushima W. Cluster of severe acute pdf (accessed May 7, 2021). respiratory syndrome coronavirus 2 infections linked to music clubs in Osaka, Japan. J Infect Dis 2020; 222: 1635–40. 17 European Centre for Disease Prevention and Controls. Heating, ventilation and air-conditioning systems in the context of COVID-19. 2020. https://www.ecdc.europa.eu/en/publications-data/heating- ventilation-air-conditioning-systems-covid-19 (accessed May 7, 2021). 1372 www.thelancet.com/infection Vol 21 October 2021