**6. The impact of genomics on public health decisions**

The emergence of SARS-CoV-2 in December 2019 triggered an unprecedented cascade of public health measures aiming at delaying the virus introduction in specific countries; prevention or limitation of viral transmission in the community; rapid tracing, identification, and isolation of contacts; and sheltering of the most vulnerable populations. These measures benefited from almost real-time surveillance of viral spread using genomic characterization.

At the beginning of the pandemic, the rapid development of sensitive real-time PCR tests was facilitated by the immediate sharing of genome sequence data. This allowed the implementation of national NAAT-based testing programs and supported the rapid diagnosis of infection, followed by preventive measures of contact tracing and isolation and quarantine – a policy known as TETRIS or TTI or TTIQ - test, track, isolate (and quarantine).

Whole genome sequencing has identified independent introduction of SARS-COV-2 from international travels, followed by local transmission clusters in individuals with no previous travel history, triggering interdictions of mass gathering and stay-at-home orders in many European countries [148, 149]. Further on, large nationwide programs of routine genetic sequencing implemented by several countries across all continents allowed for the rapid identification of new viral variants, further labeled as variants of interest (VOIs) and variants of concern (VOCs). The COG-UK consortium has identified the emergence of B.1.1.7/Alpha VOC at the end of 2020, a finding that triggered a reinstatement of lock-down in the UK [150].

Mathematical modeling of many epidemiological and social parameters were important pieces in the complicated scenarios of policymaking, as they sometimes furnished reliable predictions on the shape, amplitude, and severity of the pandemic. These parameters were adapted each time a new variant of concern was identified. In addition, genomic sequencing revealed specific mutations in the circulating viral strains that allowed rapid testing for variant monitoring – such as S target failure in a specific PCR test in the case of the Alpha VOC (B.1.1.7), due to deletion at positions 69 and 70 of the spike protein (delH69/V70). These data were conducted for a fast implementation of this biomarker in the SARS-CoV-2 community PCR testing program of Public Health England in the early autumn months of 2021 [151]. Whole genome sequencing allowed a rapid warning of the global community when variants of concern emerged and further monitoring of their dissemination and displacement of previously circulating variants. The availability of free giant repositories for whole viral genomes such as GISAID, sometimes with associated epidemiological and clinical metadata, enabled a fast follow-up of the viral spread, and thorough characterization of the variants' transmissibility and pathogenicity. For example, the genetic surveillance network in South Africa has rapidly spotted the Beta variant (B.1.351. identified in October 2020) harboring mutations associated with immune evasiveness) and the highly-mutated Omicron variant (B.1.1.529; first identified in November, 2021) [152, 153]. This information was used to back up reinforcements or

relaxations of some of the most drastic public health measures, such as lockdowns, border control, closing working places and schools, social distancing, mobility restrictions, and obligatory green passes. For example, accumulating genomic information on the spread of the highly transmissible, yet low pathogenicity Omicron variant triggered a progressive abandonment of the "zero COVID" policy with compulsory curfews, testing and strict mobility control initially adopted by a series of Eastern-Asian countries [154].

The importance of genomics for public health is underlined by the unexpected emergence of the Omicron variant, attributed either to (a) a continuous, baseline circulation of a slowly changing ancillary strain in a region with low genomic surveillance; (b) persistent infections with prolonged viral shedding and high variability in immunosuppressed persons; and (c) spill out from an unknown animal reservoir [155]. To prevent a similar episode, genomic informed public health measures must be upscaled, including:


Genomic data can inform public health policies by:

