Cytokine Response in Pregnant Women With COVID-19 Infection

Cytokines are small secreted proteins released by cells have a specific effect on the interactions and communications between cells.
In pregnant women with COVID-19, how does the severity and progression of disease affect cytokine profiles, especially towards the end of pregnancy?

The cytokine response of women in the third trimester of pregnancy to COVID-19 infection appears similar to that observed in the general population. However, certain cytokine levels differ between infected and uninfected pregnant women, and cytokine profiles over the disease course vary with clinical severity. These findings from a recent study conducted at Cornell Medicine were reported in the journal Cytokine.

It is not known whether previous research on cytokines can be applied to pregnant women, whose immune systems may react differently because of pregnancy. Researchers at Cornell wanted to find out how cytokines respond over time to the changes in severity of SARS-Cov-2 infection in pregnant women, given that research has shown that these women already have an elevated risk of severe disease and death compared with women who are not pregnant.

The investigators analyzed the serum obtained from 44 COVID-19-positive and 25 COVID-19-negative pregnant women in their third trimester admitted to a New York City hospital between March 22 and April 30, 2020. All participants were screened for COVID-19 using reverse-transcriptase polymerase chain reaction (RT-PCR) testing and underwent testing for COVID-19 symptoms upon admission to labor and delivery. The women’s vital signs and results of clinical tests were extracted from their medical records. 

The women’s serum was used to measure the following cytokines: granulocyte colony-stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin (IL)-18, IL-1ra, IL-2ra, IL-8, and interferon-gamma-induced protein (IP)-10 through enzyme-linked immunosorbent assay. The researchers compared cytokine levels between COVID-19 positive and negative groups by seronegative and seropositive infection, time since infection onset, and clinical severity.

Most participants had asymptomatic infections (27/44, 61.4%), 10 had mild or moderate illness (10/44, 22.7%), and 7 displayed severe illness (7/44, 15.9%). None were critically ill.

Cytokines IL-18, IL-1ra, and IP-10 went up in infected women compared with controls. Neverthless, no significant differences in G-CSF, HGF, IL-2Ra, or IL-8 were seen between groups. There were, however, statistically significantly differences observed by the researchers in HGF among those with severe disease and in IL-2ra among those in later stages of infection. The investigators saw no differences in cytokine levels between women who were in labor vs those who were not. The data showed that the cytokine changes were most marked in the acute phase of infection, just before seroconversion. 

High cytokine levels were noted in early infections, and higher levels correlated with more severe disease. “By [immunoglobulin M] seroconversion, IL-8 and IP-10 returned to levels seen in uninfected patients, whereas IL-18 levels stayed significantly elevated,” the authors stated.

The investigators determined that the cytokine profiles of women in their third trimester of pregnancy vary during the course of infection and correlate with clinical severity.

“Analysis by serology status revealed new patterns of the cytokine response to SARS-CoV-2 infection, that were not seen based on RT-PCR positivity or severity classifications,” the authors wrote. “Thus, the specific and differing patterns of quickly changing individual cytokine levels can be uncovered and may prove useful as markers of future disease course, outcomes, and even suggest therapeutic targets or guide timing of interventions,” they added.


Rosen DB, Murphy EA, Gejman RS, et al. Cytokine response over the course of COVID-19 infection in pregnant women. Cytokine. Published online April 25, 2022. doi:10.1016/j.cyto.2022.155894