Monoclonal Antibodies for Treatment of SARS-CoV-2 Infection During Pregnancy

  1. Erin K. McCreary
  2. Lara Lemon
  3. Christina Megli
  4. Amber Oakes
  5. Rachel L. Zapf
  6. Paula L. Kip
  7. Christopher W. Seymour

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Abstract

IMPORTANCE

Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19. However, no studies have evaluated adverse events and effectiveness of mAbs in pregnant persons compared to no mAb treatment.

OBJECTIVE

To determine the frequency of drug-related adverse events and obstetric-associated safety outcomes after treatment with mAb compared to no mAb treatment, and the association between mAb treatment and a composite of 28-day COVID-19-related hospital admission or emergency department visit, COVID-19-associated delivery, or mortality.

DESIGN, SETTING, PARTICIPANTS

Propensity-score matched cohort study of persons aged 12 years of age or older with a pregnancy episode and any documented positive SARS-CoV-2 test (polymerase chain reaction or antigen test) in the UPMC health system from April 30, 2021 to January 21, 2022.

EXPOSURES

Bamalanivmab and etesevimab, casirivimab and imdevimab, or sotrovimab treatment compared to no mAb treatment.

MAIN OUTCOMES AND MEASURES

Drug-related adverse events, obstetric-associated safety outcomes among persons who delivered, and a risk-adjusted composite of 28-day COVID-19-related hospital admission or ED visit, COVID-19-associated delivery, or mortality.

RESULTS

Among 944 pregnant persons (median [IQR] age 30 [26, 33] years, White (79.5%, N=750), median [IQR] Charlson Comorbidity Index Score 0 (0,0)), 552 persons received mAb treatment (58%). Median gestational age at COVID-19 diagnosis or treatment was 179 days (IQR: 123, 227), and most persons received sotrovimab (69%, N=382). Of those with known vaccination status, 178 (62%) were fully vaccinated. Drug-related adverse events were uncommon (N=8, 1.4%), and there were no differences in any obstetric-associated outcome among 276 persons who delivered. After propensity score matching, the frequency of the composite 28-day COVID-19-associated outcome was 4.0 per 100 persons (95% CI 1.9, 6.2) in mAb-treated compared to 3.7 per 100 persons (95% CI 1.7, 5.8) in non-treated controls (risk difference = 0.31 per 100 persons [95% CI -2.6, 3.3). There were no deaths among mAb-treated patients compared to 1 death in the non-treated controls (p = 0.24). There were more non-COVID-19-related hospital admissions in the mAb-treated persons (risk difference 2.8 per 100 persons (95% CI 1.1, 4.5)).

CONCLUSIONS AND RELEVANCE

In pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were mild and rare. There was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment among persons who delivered. MAb treatment was associated with similar 28-day COVID-19-associated outcomes and more non-COVID-19-related hospital admissions compared to no mAb treatment.

Key Points

QUESTION

Among pregnant persons with COVID-19, is monoclonal antibody (mAb) treatment associated with drug-related adverse events, similar frequency of obstetric-associated safety outcomes, and improved COVID-19-related clinical outcomes compared to no mAb treatment?

FINDINGS

In 944 pregnant persons with COVID-19, drug-related adverse events were mild and infrequent. Obstetric-associated safety outcomes were similar between mAb treatment and no treatment. There was no evidence of difference in risk of COVID-19-related hospital admission, COVID-19-associated delivery, or mortality between mAb treatment and no mAb treatment.

MEANING

In pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were uncommon, and there was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment. MAb treatment was associated with similar 28-day risk of a COVID-19-associated outcome and more non-COVID-19-related hospital admissions compared to no mAb treatment.

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  1. ScreenIT

    SciScore for 10.1101/2022.04.20.22274090: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the UPMC Quality Improvement Review Committee and University of Pittsburgh Institutional Review Board.
    Sex as a biological variableStarting September 28, 2021, pregnant patients and patients with immunocompromised conditions were given priority for mAb treatment due to drug scarcity.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Methods and results are reported in accordance with the Reporting of Studies Conducted Using Observational Routinely Collected Health Data (RECORD) statement.14 The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline (Supplement 2).
    RECORD
    suggested: (RECORD, RRID:SCR_009097)
    All analyses were performed in Stata IC, version 16 software package (StataCorp LLC), and statistical significance corresponded to a p<0.05.
    StataCorp
    suggested: None

    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:
    The study has several limitations. First, drug-related adverse events were patient and provider reported and potentially underrepresented. Second, a minority of patients completed pregnancy within the follow up period, limiting data on delivery complications and neonatal outcomes. Third, symptom severity at the time of testing and treatment (whether symptomatic or asymptomatic) was not available for non-treated patients. However, the average time from SARS-CoV-2 test result to treatment was 1 day, suggesting immortal time bias between mAb-treated and non-treated is very unlikely. Fourth, as with any observational study, these findings do not provide causal inference, as many unmeasured confounders may be present. We used multiple modeling approaches and found consistent results. Fifth, most patients in the cohort received sotrovimab when the Omicron variant was dominant in our geographic region. These data may not be generalizable to other variants, regions, or time periods.

    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.

  2. Version published to 10.1101/2022.04.20.22274090v1 on medRxiv