Review 1: "Whole Genome Sequencing Confirmed SARS-CoV-2 Reinfections Among Healthcare Workers in India with Increased Severity in the Second Episode"

Micheál Mac Aogáin

doi:doi:10.1162/2e3983f5.d1e1829e

RR:C19 Evidence Scale rating by reviewer:

Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

The study appears to represent the first genomic investigation of SARS-CoV-2 reinfection and is of interest. The authors suggest that the findings demonstrate HCWs (Health Care Workers) can get reinfected with SARS-CoV-2 with increased clinical severity in the second episode. However, it is unclear how such an assertion may be made by examining only four patients.

Data is certainly “Potentially informative;” however, there are too few samples to make firm conclusions. The data is a case series essentially.

It is potentially misleading to say that the second infection was more severe. The authors note caveats but state, “We suggest that reinfection with SARS-CoV-2 is possible, that the second episode may be more clinically severe and that this is worthy of worldwide attention and surveillance for its implications on the danger to HCWs on the frontlines of the pandemic.” I think this is somewhat misleading.

And again, here, “It was noteworthy that in all four HCWs, the first episode was asymptomatic or mildly symptomatic and the second episode was marginally more clinically severe than the first.” It was noteworthy but still needs to be confirmed in greater numbers before any conclusion can be made.

Overall, the concept is good; the sequencing and analysis seem appropriate but, clinically, the numbers are too small to draw any meaningful conclusion.