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Review 2: "Outcomes of SARS-CoV-2 Omicron infection in residents of Long-Term Care"

This preprint examines the mortality and hospitalization rates of the SARS-CoV-2 Omnicronvariant and compares them to the Delta variant. Reviewers found the study reliable but requires additional literary citations.

Published onMar 13, 2022
Review 2: "Outcomes of SARS-CoV-2 Omicron infection in residents of Long-Term Care"
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key-enterThis Pub is a Review of
Outcomes of SARS-CoV-2 Omicron infection in residents of Long-Term Care
Description

AbstractBackgroundRecently there has been a rapid, global increase in SARS-CoV-2 infections associated with the Omicron variant (B.1.1.529). Although severity of Omicron cases may be reduced, the scale of infection suggests hospital admissions and deaths may be substantial. Definitive conclusions about disease severity require evidence from populations with the greatest risk of severe outcomes, such as residents of Long-Term Care Facilities (LTCFs).MethodsWe used a cohort study to compare the risk of hospital admission or death in LTCF residents in England who had tested positive for SARS-CoV-2 in the period shortly before Omicron emerged (Delta dominant) and the Omicron-dominant period, adjusting for age, sex, vaccine type, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset.ResultsRisk of hospital admission was markedly lower in 1241 residents infected in the Omicron-period (4.01% hospitalised, 95% CI: 2.87-5.59) compared to 398 residents infected in the pre-Omicron period (10.8% hospitalised, 95% CI: 8.13-14.29, adjusted Hazard Ratio 0.50, 95% CI: 0.29-0.87, p=0.014); findings were similar in residents with confirmed variant. No residents with previous infection were hospitalised in either period. Mortality was lower in the Omicron versus the pre-Omicron period, (p<0.0001).ConclusionsRisk of severe outcomes in LTCF residents with the SARS-CoV-2 Omicron variant was substantially lower than that seen for previous variants. This suggests the current wave of Omicron infections is unlikely to lead to a major surge in severe disease in LTCF populations with high levels of vaccine coverage and/or natural immunity.Trial Registration NumberISRCTN 14447421

RR:C19 Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review:

This is an important study on the outcome of SARS-CoV-2 Omicron infection in UK Long-Term Care residents. The study design and the statistical analyses are appropriate, and the manuscript is well-written. In particular, Cox regression makes the incomplete follow-up a bit less problematic, even though additional studies with longer durations are still warranted. 

I have the following, mostly minor, comments:

1) Cohort description
The cohort is limited to the residents of LTCFs who tested positive. The rationale behind this (e.g., data constraints) should be explained in the text, as a longitudinal cohort study based on all LTCF residents would have made it possible to disentangle direct and indirect vaccine effects during the pre-omicron and Omicron-dominant periods. See also comment #3 below.

2) Table 1
Stratification of the full cohort sample (n = 1639) by period (pre-Omicron, n = 1 241 vs. Omicron-dominant period, n = 398) is lacking in Table 1. Additionally, important differences between the cases during these two periods should be commented upon in Results. Descriptive statistics for the subsets with probable and confirmed cases of Delta and Omicron could be moved to a supplementary table to avoid overloading Table 1.

3) Direct vs. indirect effects of vaccination
This is mentioned as an important limitation in the Discussion, but the authors could elaborate a bit further on this limitation. This could, for example be done by mentioning that a population-based cohort study would be required to disentangle the effects, and also by referring to studies that have tried to that (e.g., https://doi.org/10.1101/2022.02.03.22270389 , now Eurosurveillance in press)

4) Supplementary material
The referenced supplementary material of this version is lacking. I have therefore reviewed the previous version of the supplementary material, assuming that it is unchanged. Table S1 is not clear what type of p-value is used to assess the interaction (p = 0.045 for both models tested). It does not seem to be the p-value for the cross-product term. Please clarify this both in the table and in the Methods.

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