Correlation between Pregnancy Status and Severe Corona-Virus Disease Characterized by Cytokine Storm: Systematic Review and Meta-Analysis (preprint)

ABSTRACT

Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SAR2-COV-2) that identified first in Wuhan, China, in December 2019, rapidly spreading to the rest of the globe, becoming a pandemic. Some studies have eluded to an association between pregnancy status and severe COVID-19 cytokine storm, some, in contrast, have demonstrated such. The aim of the current study was to find the relationship between pregnancy status and clinical COVID-19 severity characterized by cytokine storm through a systematic review and meta-analysis approach. Methods We searched 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. The COVID-19 severity characterized by cytokine storm was described using parameters such as; Intensive Care Unit Admission, Invasive Mechanical Ventilation, Mechanical Ventilation, Hospital Admission, Pro and Inflammatory cytokine levels, consolidation on chest CT scan, pulmonary infiltration, extreme fevers as characteristic of cytokine storm, syndromic severity, higher neutrophil count indicative of cytokine storm and severe COVI-19 presentation. Results A total of 17 articles detailing 840332 COVID-19 women were included. Our meta-analysis revealed a relationship between positive pregnancy status and severe COVID-19 cytokine storm case (random effect model, OR=2.47; 95% CI 1.63-3.73; P < 0.0001), with a cumulative incidence of 6432 (14.1%) among the pregnant women with COVID-19 and 24352 (3.1%) among the non-pregnant women with COVI-19. Further to this, we found that the sub-analysis between Single Centre and Multiple Centre studies demonstrated seemingly the same as heterogeneity (I 2 = 72 and (I 2 = 98), respectively. Sensitivity analysis on each sub-group revealed that pregnancy was significantly related to severe COVID-19 with cytokine storm from single Centre studies, (fixed effect model, OR= 3.97; 95% CI 2.26-6.95; P< 0.00001) with very low heterogeneity (I 2 = 2 %; P = 0.42). Conclusion Being pregnant is clearly associated with experiencing a severe COVID-19 characterized by a cytokine storm. The SARS-COV-2 epidemic should serve as an impetus for pregnant women diagnosed with COVID-19, and map out salient risk factors associated with its severity. The trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) CRD42021242011.