Real-World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients

  1. Neil R Aggarwal
  2. Laurel E Beaty
  3. Tellen D Bennett
  4. Nichole E Carlson
  5. Christopher B Davis
  6. Bethany M Kwan
  7. David A Mayer
  8. Toan C Ong
  9. Seth Russell
  10. Jeffrey Steele
  11. Adane F Wogu
  12. Matthew K Wynia
  13. Richard D Zane
  14. Adit A Ginde

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Abstract

Background

It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) patients, is also effective in preventing the progression of severe disease and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection.

Methods

In an observational cohort study of nonhospitalized adult patients with SARS-CoV-2 infection, 1 October 2021–11 December 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data, we used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization.

Results

Of 10 036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% vs 5.7%; adjusted odds ratio [aOR], 0.37; 95% confidence interval [CI], .19–.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% vs 1.0%; aOR, 0.11; 95% CI, .0–.79), and may reduce respiratory disease severity among those hospitalized.

Conclusions

Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

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  1. Version published to 10.1093/infdis/jiac206
  2. ScreenIT

    SciScore for 10.1101/2022.04.03.22273360: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the Colorado Multiple Institutional Review Board with a waiver of informed consent.
    Consent: The study was approved by the Colorado Multiple Institutional Review Board with a waiver of informed consent.
    Sex as a biological variablenot detected.
    RandomizationWhen mAb treated patients were missing a SARS-CoV-2 positive date (70.5%), we randomly imputed missing test dates from the distribution of observed time between SARS-CoV-2 to mAb administration.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Limitations: This study has several limitations. The setting was a single health system and geographically limited to one US state with relatively low racial and ethnic minority representation, though it serves both urban and rural populations through academic and community hospitals. Even though we used statewide data for mortality and vaccination status, hospitalizations were collected only within one single health system. If mAb-untreated patients were less likely to be seen in this health system, hence more likely to be hospitalized elsewhere, this may bias our results toward the null. We also relied on EHR data, including manual chart reviews, which may have missing or inaccurate information about the presence of chronic conditions.[23] These factors might have limited our ability to detect the impact of sotrovimab treatment. We only collected 28-day hospitalization and mortality data, and therefore we do not know whether sotrovimab effectiveness extends to a longer period after SARS-CoV-2 infection. However, our prior study would suggest that 28-day and 90-day data are similar with respect to hospitalization and mortality endpoints.[7] In this study, propensity scoring achieved excellent matching between mAb-treated and mAb-untreated patient groups across multiple variables, but unmeasured confounders may remain. Our EHR data does not contain information on SARS-CoV-2 variants at the patient level. However, during Colorado’s Delta phase more than 99% of sequenced SARS-C...

    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.

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  3. Version published to 10.1101/2022.04.03.22273360 on medRxiv