Review 1: "Equity and Efficiency in Global Respiratory Virus Genomic Surveillance"

RR:C19 Evidence Scale rating by reviewer:

• Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: Overall, I think this paper is very good, I would just highlight a few points where additional nuance is required.

Global variant detection (line 129 onwards) – this is interesting and logical, but I think it’s worth mentioning that travel patterns are really important here. If a low-surveillance country has strong connections to a high-surveillance country, the variant will be detected faster than if it mostly has connections to another low-surveillance country. It doesn’t change the salient point of the paragraph, but just to highlight that not all intercontinental spread leads to similar delays when genomic surveillance is patchy.

As a note on the emergence of Alpha variant – I would argue that epidemiological data was accruing already in November with the increase of cases in the South-East of England despite lockdown. It was noticed in December initially, but that was because variants were new. There’s therefore an additional part this puzzle that is the ability to notice what is happening and what to look for. For example, when Omicron variant emerged, it was noticed much faster with far fewer numbers of sequences because it was known to look for these long phylogenetic branches as a signature for an incoming variant. This doesn’t negate the point at all, but just to add nuance.

I understand why variant detection is the focus here, but I think it’s important to highlight that the size of dataset required depends heavily on the question being asked of the dataset. For example, the authors suggest reducing sequencing output, but then highlight Alpha variant detection. Due to the high output of sequencing in the UK, an intermediate sequence in the evolution of Alpha variant was found which provides important clues in the role of different mutations in the epistatic interactions in the evolution of variants. Further, detailed phylogenetic analyses often require larger datasets, and this was again possible in the UK (and other countries). In the discussion of sequencing as a public good, I think it shouldn’t be missed that increased infrastructure investment in one country can provide fundamental information on the spread and evolution of a pathogen beyond detection. This doesn’t remove the main point of the article of the baseline of sequencing globally would vastly benefit everyone, but I think suggesting the reduction of sequencing is a bit narrow and so it should be highlighted that it strongly depends on what someone hope to get from their sequence dataset, and that more fundamental genomic science has an important role in disease control.