Outbreaks with viruses occur continuously, and novel viruses or new variants of existing viruses can surface after a zoonotic event or human-to-human transmission. This project proposal is designed to detect early circulation of (novel) respiratory viruses in both symptomatic and asymptomatic participants, either by direct detection of the virus or changes in local or systemic immunity. Additionally, SENTINEL will provide information on infectivity and (protective) immune responses in viral outbreaks or vaccination campaigns.

A well-designed surveillance study in specific cohorts can serve as an early warning system for (1) the introduction of novel viruses (or variants) in the human population, (2) viral immune escape from pre-existing immunity, or (3) virus evolution into more pathogenic variants. Here, we propose prospective sampling of two sentinel groups with high-risk-of exposure to circulating respiratory viruses for the monitoring of both symptomatic and asymptomatic infections, and immune responses to those infections. Hospital staff (HCW) were shown to be good sentinels for the early detection of respiratory viruses, due to their close contact with patients (or colleagues) with respiratory symptoms. Previous studies in HCW during the COVID-19 pandemic have shown that they are a motivated study population, in which sampling at multiple time-points is feasible if the location is close to work and easily accessible. Other interesting sentinels for respiratory viruses are animal workers (AW), as they are exposed to various animal species and infectious viruses, including respiratory viruses with zoonotic potential. History has shown that most major disease outbreaks were preceded by animal-to-human transmission events that remained undetected until large scale human-to-human transmission occurred. The COVID-19 outbreak is the most recent and devastating example. Similarly, the current extensive transmission of influenza virus H5Nx is of concern and has already spilled over into humans on several occasions. Widespread transmission spillover events to mammals could allow the virus to gain mammalian adaptation. In this prospective SENTINEL study, we propose (self)-sampling of participants (starting just before the 2024 respiratory season), during symptomatic infections to identify and genomically characterize the causative respiratory virus. Follow-up visits will be planned to monitor induced local and systemic immune responses. In addition, we propose periodic sampling of participants to assess changes in local and systemic immune parameters caused by unnoticed/asymptomatic infections with respiratory viruses. Finally, participants will be invited for follow up visits after vaccination against respiratory viruses to monitor vaccine induced responses.

This proposal is unique, as we propose to establish biobanks that include paired samples from the upper respiratory tract and peripheral blood, allowing us to study both local and systemic immunity after infection and/or vaccination. More knowledge on local immunity could be crucial for future vaccine design, and application of vaccines in the respiratory tract. SENTINEL will establish a framework that facilitates early detection of viruses that would otherwise stay under the radar until surfacing due to large scale human-to-human transmission. The rapid genomic characterization and isolation of infectious virus will support rapid development of diagnostic assays, giving a head start in case of (re)emergence of a respiratory virus. Additionally, collecting clinical samples over a prolonged period will yield a valuable biobank of blood samples, respiratory tract samples and viruses, of crucial value for future research and/or (retrospective) analysis of respiratory viruses and immune responses directed against these viruses.

Inclusion Criteria:

• 18 years or older
• Health care workers with or without direct patient contact
• Animal workers with or without direct animal contact

Exclusion Criteria:

• <18 years

Individuals working at healthcare facilities or facilities with animals (e.g. farms, bird ringers, or slaughterhouses). We will include an average of 250 participants per year, over a maximum of 5 years. 1,000 participants will be recruited in total for the study.