How could SARS-CoV-2 viral infection modulate the immune landscape during the active infection phase and recovery in pregnant females?

In a recent article published in the bioRxiv* preprint server, researchers examined immune reflexes towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant women.

Study: Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women. Image Credit: Natalia Deriabina/Shutterstock
Study: Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women. Image Credit: Natalia Deriabina/Shutterstock

Background

Pregnancy is a complicated process, and women's immune systems fluctuate significantly during this time. The SARS-CoV-2 viral infection places further strain on the already overworked immune system.

Some research has demonstrated that pregnant females are not vulnerable to coronavirus disease 2019 (COVID-19) or have severe SARS-CoV-2 symptoms. On the contrary, some studies have suggested that age-matched pregnant ladies are more susceptible to COVID-19 than typically healthy non-pregnant women. Besides, it is unclear why there is a disparity in the data on the immune reactions of SARS-CoV-2-infected pregnant women.

About the study

In the present cross-sectional research conducted in Malaysia, the researchers explored how SARS-CoV-2 infection could change the immune environment in the active infection stage and recovery among pregnant females. The team used flow cytometry and single-cell ribonucleic acid sequencing (scRNA-seq) to evaluate how the SARS-CoV-2 infection can modify the immune reaction in pregnant women during the active SARS-CoV-2 infection and after COVID-19 recovery.

Further, 21 pregnant ladies who met the exclusion and inclusion standards were recruited for the study via convenience sampling. The study's eligibility requirements were age above 18 years, a positive reverse transcription polymerase chain reaction (RT-PCR) result for the SARS-CoV-2-infected pregnant cohort, and a negative RT-PCR result for healthy controls and pregnant women who had recovered from COVID-19. Before enrolling, the 21 study subjects, including 13 healthy pregnant controls, four pregnant COVID-19 survivors, and four pregnant SARS-CoV-2-infected women, submitted written informed consent.

The scientists procured blood samples from the 21 study volunteers. The severity of COVID-19 for the analysis was based on symptoms. The participants were selected from the outpatient clinical wards of the obstetrics and gynecology clinic between April 2020 and February 2021. The authors followed the Declaration of Helsinki while performing the study methods.

Results

In the current report, the scientists discovered the immune fingerprint in SARS-CoV-2 infected and COVID-19-recovered pregnant ladies utilizing scRNA-seq and multi-color flow cytometry. The multi-color immunophenotyping information implies the presence of a pattern of reduced monocytes among SARS-CoV-2-infected and recovered pregnant women relative to healthy pregnant females. It also depicts a substantial decline in the proportion of total lymphocytes in these two cohorts.

In addition, profiling of CD8+ T cells or CD4+ T cells showed a higher proportion of late or early effector CD8+ T cells across pregnant COVID-19-infected women versus pregnant convalescent SARS-CoV-2 patients. The effector cells of the CD4+ T cells also showed a similar pattern. Nevertheless, when comparing healthy control pregnant women with SARS-CoV-2-infected pregnant women, a decreased tendency of effector cells, either CD8+ or CD4+ T cells, was also seen. These results suggest that viral infection causes a temporary decrease in effector cells, which increases proportionately following the clearance of the virus.

Relative to healthy pregnant ladies, natural killer (NK) cells were generally lower in COVID-19-infected and recovered pregnant women. According to the phenotyping results, reduced NK cells and effector T cells during an active COVID-19 event could prevent an aggravated immune response.

Moreover, SARS-CoV-2 infection had altered the gene expression pattern of CD4+ effector cells, antibody-secreting B cells, and monocytes in pregnant convalescent COVID-19 patients as opposed to healthy pregnant females, according to the single-cell RNA sequencing information. SARS-CoV-2-recovered pregnant ladies exhibited impaired levels of various genes harboring cytotoxic function, type I and II interferon signaling, and anti- and pro-inflammatory activities across NK cells and CD8+ cytotoxic T cells compared to healthy pregnant ladies.

Conclusions

Collectively, the authors found that pregnant women who recovered from COVID-19 compared to those who were presently virus-infected displayed higher levels of intermediary effector CD8+ T cells by applying flow cytometry. Likewise, relative to COVID-19-infected pregnant females or healthy pregnant ladies, the recovery phase showed a rise in CD4+ T helper cells (early or late). On the other hand, virus-infected pregnant women exhibited a decreased number of late effector CD4+ T cells. Contrary to healthy pregnant females, COVID-19-recovered pregnant women had a substantial hike in CD3+CD4-CD8-NKT cells, which dropped during active infection.

Additionally, the scRNA-seq assessment indicated a definite molecular benefit for SARS-CoV-2-infected recovered women to prevent pregnancy complications. Yet, more extensive research was required to verify these facts and findings. 

Overall, the current study shows how SARS-CoV-2 infection disrupted pregnant women's adaptive immune responses and may have been a factor in ongoing pregnancy complications.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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