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Association of Pregnancy With Coronavirus Cytokine Storm: Systematic Review and Meta-analysis

John Muthuka¹, Michael Kiptoo², Kelly Oluoch¹

¹Head Quaters, Kenya Medical Training College, Nairobi, Kenya.

JMIR Pediatrics and Parenting

|March 23, 2022

Insights

Pregnancy is linked to a higher risk of severe COVID-19 and cytokine storm. This systematic review and meta-analysis confirms this association, highlighting the need for further research in pregnant women.

Area of Science:

Infectious Diseases
Immunology
Obstetrics & Gynecology

Background:

COVID-19 pandemic has raised concerns about its impact on pregnant individuals.
Conflicting evidence exists regarding the association between pregnancy and severe COVID-19 outcomes, specifically cytokine storm.
This study addresses the need for a comprehensive analysis of this relationship.

Purpose of the Study:

To systematically review and meta-analyze the relationship between pregnancy status and severe COVID-19 characterized by cytokine storm.
To quantify the risk of severe COVID-19 with cytokine storm in pregnant versus non-pregnant women.

Main Methods:

Systematic literature search across major databases (Google Scholar, PubMed, Scopus, Web of Science, Embase).
Inclusion of clinical studies comparing COVID-19 severity (cytokine storm indicators) in pregnant and non-pregnant women.
Meta-analysis using random-effects and fixed-effects models to assess the association and heterogeneity.

Main Results:

Analysis of 17 articles involving 840,332 women with COVID-19.
Significant correlation found between pregnancy and severe COVID-19 with cytokine storm (OR 2.47, P<.001).
Cumulative incidence of severe COVID-19 with cytokine storm was 14.1% in pregnant vs. 3.1% in non-pregnant women. Heterogeneity was addressed through updated analysis and subanalyses.

Conclusions:

Pregnancy is significantly associated with a severe COVID-19 course featuring a cytokine storm.
The findings underscore the importance of prioritizing research on COVID-19 in pregnant populations.
Further investigation is crucial to identify specific risk factors for severe COVID-19 in pregnant women.

Read full analysis

Abstract

Background:

COVID-19 was first identified in Wuhan, China, in December 2019, spreading to the rest of the globe, becoming a pandemic. Some studies have shown an association between pregnancy status and severe COVID-19 with a cytokine storm, whereas others have shown contrasting results.

Objective:

The aim of this study was to examine the relationship between pregnancy status and the clinical COVID-19 severity characterized by the cytokine storm through a systematic review and meta-analysis.

Methods:

We searched the Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting pregnancy status and comparing the COVID-19 severity cytokine storm outcome were included. COVID-19 severity characterized by a cytokine storm was described using parameters such as intensive care unit admission, invasive mechanical ventilation, mechanical ventilation, hospital admission, pro- and anti-inflammatory cytokine levels, consolidation on chest computed tomography scan, pulmonary infiltration, extreme fevers as characteristic of a cytokine storm, syndromic severity, higher neutrophil count indicative of a cytokine storm, and severe COVID-19 presentation.

Results:

A total of 17 articles including data for 840,332 women with COVID-19 were included. This meta-analysis revealed a correlation between positive pregnancy status and severe COVID-19 with a cytokine storm (random-effects model odds ratio [OR] 2.47, 95% CI 1.63-3.73; P<.001), with a cumulative incidence of 6432 (14.1%) and 24,352 (3.1%) among pregnant and nonpregnant women with COVID-19, respectively. The fixed-effects model also showed a correlation between pregnancy status and severe COVID-19 with a cytokine storm (OR 7.41, 95% CI 7.02-7.83; P<.001). Considerable heterogeneity was found among all pooled studies (I²=98%, P<.001). Furthermore, the updated analysis showed substantially low heterogeneity (I²=29 %, P=.19), and the funnel plot revealed no publication bias. The subanalysis between single-center and multicenter studies demonstrated similar heterogeneity (I²=72% and 98%, respectively). Sensitivity analysis on each subgroup revealed that pregnancy was significantly related to severe COVID-19 with a cytokine storm from single-center studies (fixed-effects model OR 3.97, 95% CI 2.26-6.95; P<.001) with very low heterogeneity (I²=2%, P=.42).

Conclusions:

Being pregnant is clearly associated with experiencing a severe course of COVID-19 characterized by a cytokine storm. The COVID-19 pandemic should serve as an impetus for further research on pregnant women diagnosed with COVID-19 to map out the salient risk factors associated with its severity.

Trial Registration:

PROSPERO CRD42021242011; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242011.

Keywords:

COVID-19 coronavirus cytokine cytokine storm immune response infectious disease maternal health pandemic pregnancy pregnant respiratory virus

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