Dear Editor, The ongoing FIFA World Cup 2022 hosted by Qatar is one of the most popular and largest international mass gathering (MG) sports events in the world1. Genomic investigations over the past year have revealed cryptic, ominous transmission of severe acute respiratory syndrome coronavirus 2, monkeypox, poliovirus, influenza, and antibiotic-resistant microbes at MG events. Qatar’s public health authorities have spent a lot of time and effort preparing and planning to ensure the health and safety of millions of international and national spectators, athletes, and organizers. However, there are still several major public health challenges, both perceived and real, that threaten global health security. The FIFA World Cup in 2022 is taking place during the ongoing global outbreaks of coronavirus disease 2019, monkeypox, antibiotic-resistant bacteria, influenza, respiratory syncytial virus, and drug-resistant tuberculosis, among others. Recently, a new hybrid virus formed from fusion of influenza A and respiratory syncytial virus is a worrying development2. Therefore, the risk of transmission of infectious diseases, amplification, and local and international spread of known and unknown pathogens during and after the FIFA World Cup remains significant. Historically, pathogens transmitted by the waterborne and fecal-oral routes have been evaluated through wastewater-based surveillance (WBS)3. Wastewater surveillance is more sensitive and cost-effective than clinical or epidemiological surveillance4. WBS was used in the polio eradication effort and has most recently been used for tracking the spread of severe acute respiratory syndrome coronavirus 2 and its variants2. In particular, there is no consensus on wastewater monitoring techniques and standardized global protocols for collecting and analyzing data4. There remains an urgent need to develop a global consensus for standardized global guidelines for sampling methods, sample pretreatment, and quantification, which is very practical at these times. WBS for pre-empting potential disease outbreaks could provide crucial information when used together with rapid detection laboratory techniques such as genomics and biosensors5,6. Early detection of disease outbreaks during MG events provides host countries with unique opportunities to develop evidence-based decisions for timely scientific-based public health interventions. Since a sample of wastewater reflects the entire contributing population, wastewater-based epidemiology can be used to learn about the spread of gastrointestinal and other viruses at the community level without the need to test many people7. Independent of the appearance of clinical symptoms or socioeconomic biases related to case reporting, WBS has been shown to be effective in detecting infection and transmission in the population. Adopting wastewater surveillance for infectious diseases during the FIFA World Cup 2022 and other future MG events could serve as an important tool to early alert the host country and global public health authorities (Fig. 1). Movements of attendees of MG events across Qatari municipalities should be wastewater-based epidemiology-based decisions, and consequent vaccination, countermeasures, and nonpharmaceutical interventions could be required. The wastewater-based epidemiology enabled Qatar officials to conduct a health survey during tournament days at a community level. Furthermore, it would give other countries an indication of potential pathogens being brought in by returning travelers8. WBS provides a powerful platform for detecting emerging and re-emerging viruses, antimicrobial resistance pathogens, and antimicrobial resistance genes. Its potential to alert host countries and global health authorities to imminent or emerging waterborne disease will add further to preparedness and proactive prevention control plans in place. Ultimately, this perspective is novel for MGs in the midst of mega sporting events, which should be further studied and considered.Figure 1: Wastewater surveillance as an epidemiological tool amidst the mega sporting events.Ethical approval Not applicable. Sources of funding None. Authors contribution A.R.A.S., A.A.M., P.C., and O.P.C. developed the original draft; A.M., B.K.P., and R.S. reviewed and edited the manuscript. All authors read and approved the final manuscript. Conflict of interest The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor R. Sah.