The role of Extracellular vesicles in COVID-19 infection during pregnancy

Ayelet Dangot ^1,2,4 Mor Zavaro ^1,4 Tali Barlev ¹ Ayala Zilberman ² Irit Avivi ^3,4 Anat Aharon ^1,3,4

¹Hematology Division, Hematology Research Laboratory for Extracellular Vesicles, Tel-Aviv Sourasky Medical Center, Israel
²Obstetrics and Gynecology Department, Lis Hospital for Women, Tel Aviv Sourasky Medical Center, Israel
³Hematology Division, Tel-Aviv Sourasky Medical Center, Israel
⁴Sackler Faculty of Medicine, Tel Aviv University, Israel

SARS-CoV-2 infection during pregnancy is associated with adverse outcomes, especially in severe disease. Most pregnant women experience a mild disease with good outcomes. Trophoblast cells line the placenta, releasing extracellular vesicles (EVs) into maternal circulation, regulating maternal immune response.

The study aimed to characterize EV population in women infected with SARS-CoV-2 during pregnancy as a predictor of disease severity.

Methods: EVs were isolated from platelet poor plasma obtained from 22 pregnant women infected with SARS-CoV-2 (CoV-P), 16 healthy pregnant (HP) and 10 non-pregnant (NP) controls. EVs size/concentration, origins, coagulation factors and cytokine content were assessed, using Nano tracking analysis (NTA), Flow cytometry and western Blot.

Results: Plasma from CoV-P subjects contained a lower concentration of EVs compared to HP, with a higher expression of exosome markers (CD63 and CD81). EVs did not indicate a cytokine storm. IL-6 and IL-2 levels decreased in EVs of CoV-P subjects compared to HP. Elevation of CD8+ T cells was seen in EVs of CoV-P subjects, especially in severe cases, in contrast to the literature describing severe COVID-19 patients. EVs expressing monocytes marker (CD14) were elevated in severe CoV-P subjects, indicating more severe infection. EVs coagulation markers/activity were similar in HP and CoV-P.

In summary, COVID-19 infection during pregnancy displays an attenuated immune response compared to what has been reported in non-pregnant COVID-19 patients. The expected disease course characterized by “cytokine storm” and hypercoagulability, are moderated in the CoV-P subjects. This phenomenon may be attributed to the role of the placenta in mitigating immune regulation.