Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study

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Abstract

Background

The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

Methods

Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination.

Results

In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40–4.26), Beta (HR 2.85, 95% CI 1.56–5.23), Delta (HR 2.28 95% CI 1.56–3.34), or Alpha (HR 1.64, 95% CI 1.29–2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56–1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination.

Conclusions

Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Article activity feed

  1. Sergey Yegorov

    Review 2: "Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study"

    This preprint claims that, although vaccination may reduce the risk, infection with VOC results in a higher hospitalization risk. Both reviewers found it to be reliable but suggested an adjustment for calendar time in the primary analysis would have produced a better output.

  2. Oliver Stirrup

    Review 1: "Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study"

    This preprint claims that, although vaccination may reduce the risk, infection with VOC results in a higher hospitalization risk. Both reviewers found it to be reliable but suggested an adjustment for calendar time in the primary analysis would have produced a better output.

  3. SciScore for 10.1101/2021.09.29.21264272: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationLaboratories and the percentage of randomly selected positive specimens they submit for sequencing were designated to optimize representation across the state.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using R version 3.6.2 (R Project for Statistical Computing).
    R Project for Statistical
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Given our sample size limitations, we then analyzed the association between vaccination and risk of hospitalization after adjusting with relevant covariates but without stratification by lineage. Due to the observational nature of our study, our vaccination findings are subject to collider stratification bias, making the magnitude of effects difficult to interpret, although we expect the bias to work in a conservative fashion, resulting in underestimates of vaccine protection on hospitalization risk. We find that cases with an active vaccination (≥21 days post dose one) have a lower risk of hospitalization when compared to those without a history of vaccination, which are consistent with estimates from Public Health Scotland (HR 0.34, 95% CI 0.23–0.50, vs. HR 0.32, 95% CI 0.22–0.46, respectively). In order to increase the power of our analysis, we aggregate cases with a Pfizer–BioNTech or Moderna, or Johnson & Johnson vaccination into a singular vaccination category. While studies have shown similar findings for the two mRNA vaccines in regards to efficacy against ancestral lineages (25,26), a study from Qatar showed differences in effectiveness between the two vaccines against infection with the Alpha and Beta lineages (27), potentially impacting the generalizability of our aggregated findings. Further studies more adequately powered to analyze the difference between vaccine formulations are urgently needed. Previous studies that examine differences in risk of hospitalizatio...

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.