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Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3320 (Published 01 September 2020) Cite this as: BMJ 2020;370:m3320

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Evidence based care for pregnant women with covid-19

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SARS-CoV-2 might affect placental function in pregnant females

Dear Editor,

We like to thank John Allotey et al. (1) for their excellent, comprehensive and elaborate study investigating the risk factors and maternal and perinatal outcomes in pregnant women with suspected or confirmed COVID-19 disease. Not only will this meta-analysis be useful for clinical decision making in the current pandemic, but it will also make a frame-work for unforeseen future communicable diseases that involve maternal and child health. In this regard, we like to share the findings from one of our studies exploring the role of SARS-CoV-2 during pregnancy and its effect on placentation and feto-maternal interactions.

Using an in-silico based approach (2) based on the initial findings by Gordon et al. (3), who identified 332 host proteins that could potentially interact with 26 of the 29 SARS-CoV-2 proteins, we investigated the potential interaction between SARS-Cov-2 viral proteins and proteins involved during trophoblast invasion and differentiation, two critical obligatory steps during placentation. Eight data-sets from NCBI-GEO related to trophoblast functions were interrogated to estimate the possible interactions with CoV-2. Preliminary information from our study (2) adds on to the observation and the clinical outcome as reported by Allotey et al. We did find significant trophoblast-virus cross-talks in the interactome that were enriched during the process of trophoblast invasion into the endometrium, spiral artery remodeling, and trophoblast differentiation. Based on our study, we thus speculate that COVID-19 could also affect the developing conceptus and lead of pregnancy-related complications.

The major consensus at this stage of COVID-19 is the lack of substantial evidence for vertical transmission of SARS-Cov-2, like the predecessor coronaviruses causing SARS and MERS (4,5). However, there is one report on a probable case of vertical transmission (6). SARS-CoV-2 infection in the third trimester of pregnancy was found to be associated with an increased risk of preterm delivery and intrauterine fetal distress and the requirement for Caesarean sections (7), similar to the observations reported by Allotey et al. of a higher preterm birth rate amongst females with COVID-19 as compared to those without the infection.

We, therefore, recommend a more rigorous and detailed investigation to study SARS-CoV-2 disease on the developing fetus, the material of conceptus in aborted cases, as well as establishing suitable animal models to address this otherwise un-explored aspect of pregnancy in COVID -19 infection.

Conflict of Interest: None
Authors: Ruby Dhar 1, Ashikh Seethy 1 and Subhradip Karmakar 1*
*Corresponding: Dr. Subhradip Karmakar : E-mail: subhradip.k@aiims.edu
Associate Professor and Group Leader
1 Room 3020, Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India

Dr Ruby Dhar (rubydhar@gmail.com)
Scientist
1 Room 3020, Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India

Dr Ashikh Seethy (ashikh.seethy@gmail.com)
Clinical Research Fellow

References:
1. Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. Published 2020 Sep 1. doi:10.1136/bmj.m3320
2. Seethy, A.A.; Singh, S.; Mukherjee, I.; Pethusamy, K.; Purkayastha, K.; Sharma, J.B.; Dhar, R.; Karmakar, S. An In Silico Analysis of Potential SARS-CoV-2 Interactions with Proteins Involved in Placental Functions. Preprints 2020, 2020050333 (doi: 10.20944/preprints202005.0333.v1).
3. D.E. Gordon, G.M. Jang, M. Bouhaddou, J. et al SARS-CoV-2 protein interaction map reveals targets for drug repurposing, Nature. (2020) 1–13. https://doi.org/10.1038/s41586-020-2286-9.
4. D. Sutton, K. Fuchs, M. D’Alton, D. Goffman, Universal Screening for SARS-CoV-2 in Women Admitted for Delivery, N. Engl. J. Med. 0 (2020) null. https://doi.org/10.1056/NEJMc2009316.
5. P. Dashraath, J.L.J. Wong, M.X.K. Lim, L.M. Lim, S. Li, A. Biswas, M. Choolani, C. Mattar, L.L. Su, Coronavirus disease 2019 (COVID-19) pandemic and pregnancy, Am. J. Obstet. Gynecol. (2020). https://doi.org/10.1016/j.ajog.2020.03.021.
6. J. Qiao, What are the risks of COVID-19 infection in pregnant women?, Lancet Lond. Engl. 395 (2020) 760–762. https://doi.org/10.1016/S0140-6736(20)30365-2
7. L. Dong, J. Tian, S. He, C. Zhu, J. Wang, C. Liu, J. Yang, Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn, JAMA. (2020). https://doi.org/10.1001/jama.2020.4621.

Competing interests: No competing interests

08 September 2020
Subhradip Karmakar
Associate Professor; Group Leader
Ruby Dhar, Ashikh Seethy
All India Institute of Medical Sciences, New Delhi, India
Room 3020, Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India