Intravenous Immunoglobulin (IVIG) Significantly Reduces Respiratory Morbidity in COVID-19 Pneumonia: A Prospective Randomized Trial

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Abstract

Background

Interventions mitigating progression to mechanical ventilation in COVID-19 would markedly improve outcome and reduce healthcare utilization. We hypothesized that immunomodulation with IVIG would improve oxygenation and reduce length of hospital stay and progression to mechanical ventilation in COVID-19 pneumonia.

Methods

Patients with COVID-19 were randomized 1:1 to prospectively receive standard of care (SOC) plus IVIG 0.5 g/kg/day × 3 days with methylprednisolone 40 mg 30 minutes before infusion versus SOC alone.

Results

16 subjects received IVIG plus SOC and 17 SOC alone. The median age was 51 years for SOC and 58 years for IVIG. APACHE II scores and Charlson comorbidity indices were similar for IVIG and SOC (median 7.5 vs 7 and 2 for both, respectively). Seven SOC versus 2 IVIG subjects required mechanical ventilation (p=0.12, Fisher exact test). Among subjects with A-a gradient of >200 mm Hg at enrollment, the IVIG group showed i) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p=0.038 Fisher exact test), ii) shorter median hospital length of stay (11 vs 19 days, p=0.01 Mann Whitney U), iii) shorter median ICU stay (2.5 vs 12.5 days, p=0.006 Mann Whitey U), and iv) greater improvement in PaO 2 /FiO 2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], p=0.01, Mann Whitney-U test) than SOC.

Conclusion

This pilot prospective randomized study comprising largely of Latino patients showed that IVIG significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in COVID-19 patients with A-a gradient >200 mm Hg.

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  1. SciScore for 10.1101/2020.07.20.20157891: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The research protocol was approved by the Internal Review Board of the participating hospitals prior to patient enrollment and was registered on clinicaltrials.gov (April 28, 2020;; NCT04411667).
    Consent: All participants provided informed consent electronically.
    RandomizationStudy design: This was an open-label randomized controlled trial performed at two hospital centers: Sharp Memorial Hospital (San Diego, CA) and Sharp Grossmont Hospital (La Mesa, CA).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot 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:
    This study has some important limitations. First, this study was performed in just 2 hospitals in one US city, resulting in a fairly homogenous population of younger Latino patients where results may not automatically translate to other patient settings. Secondly, while prospective and randomized, the study was not blinded and therefore subject to bias. This was reduced by the fact that the clinical investigators had minimal clinical decision-making on these patients, particularly regarding the endpoints of mechanical ventilation and discharge from the hospital. Third, the concomitant use of methylprednisolone therapy may have confounded the results. At the time of study initiation, the use of glucocorticoid therapy was controversial, possibly causing harm in COVID-19. We decided to give methylprednisolone 40 mg (equivalent to approximately 7·5 mg dexamethasone) to mitigate any potential adverse effects of IVIG such as headache, theorizing that benefit would outweigh risk by increasing tolerability of IVIG. Just recently, however, the benefit of glucocorticoid therapy was shown with 6 mg of dexamethasone for 10 days.30 While there may have been a small benefit rendered by this premedication, it is unlikely that the difference in outcomes between the two groups rested on this intervention. This is supported by the fact that the benefits of IVIG were significant even when comparison was made to the subset of SOC patients that received glucocorticoid therapy. Fourth, the sample ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04411667Active, not recruitingStudy of SOC Plus IVIG Compared to SOC Alone in the Treatmen…
    NCT04400058CompletedOctagam 10% Therapy in COVID-19 Patients With Severe Disease…


    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.

    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.