Immunological mechanisms of SARS-CoV-2 infection in gestational complications
DOI:
https://doi.org/10.33448/rsd-v11i4.27654Keywords:
Immunological Factors; Gestational complications; COVID-19; Pregnancy Result.Abstract
Objective: To analyze and synthesize the main immunological mechanisms related to greater severity or worse outcome in pregnant women infected with SARS-CoV-2. Methods: This is a systematic literature review that was performed by searches on Medline (by PubMed), from October 2021 to January 2022, using the descriptors Pregnancy complications; Immunological Factors; SARS-CoV-2, Covid-19, which aimed to answer the question: “Which immunological mechanisms are related to greater severity or worse outcome in pregnant women infected with SARS-CoV-2?”. Original manuscripts, written in English language and published from 2020 onwards were chosen. Reviews or meta-analyses, editorials and duplicate titles were excluded. The search resulted in 189 articles, of which 11 were selected for matching the eligibility criteria. Results: Changes were found in the immunological functioning of the pregnant organism that may predispose the pregnant woman to a greater susceptibility to SARS-CoV-2 infection and to a more severe course of the disease. These alterations include reduced levels of Natural Killer cells and T helper cells type 1, in addition to an increase in the hyperinflammatory state related to excessive activation of the complement system and an increase in pro-inflammatory cytokines, such as interleukin-6 and α tumor necrosis factor. Besides the increase in angiotensin-converting enzyme 2 in maternal circulation leads to increased viral binding in the host cell and infectivity. Conclusion: Due to the impact that immunological mechanisms have on the evolution of COVID-19 disease on maternal health, it is evident the importance of identifying the elevation of these immunological biomarkers, which can help in the prediction of maternal prognosis and in the definition of appropriate early treatment.
References
Abu-Raya, B., Michalski, C., Sadarangani, M., & Lavoie, P. M. (2020). Maternal Immunological Adaptation During Normal Pregnancy. Frontiers in Immunology, 11, 575197. https://doi.org/10.3389/fimmu.2020.575197
Benton, D. J., Wrobel, A. G., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020). Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. Nature, 588(7837), 327–330. https://doi.org/10.1038/s41586-020-2772-0
Cavalcante, M. B., Cavalcante, C. T. de M. B., Sarno, M., Barini, R., & Kwak-Kim, J. (2021). Maternal immune responses and obstetrical outcomes of pregnant women with COVID-19 and possible health risks of offspring. Journal of Reproductive Immunology, 143, 103250. https://doi.org/10.1016/j.jri.2020.103250
Chen, Y., Pang, X., Ding, W., Peng, X., Yang, J., & Zhou, Y. (2021). Retrospective Analysis of Clinical Characteristics and Neonatal Outcomes of Pregnant Women with SARS-COV-2 Infection. Current Medical Science, 41(2), 306–311. https://doi.org/10.1007/s11596-021-2347-9
Choe, P. G., Kim, K.-H., Kang, C. K., Suh, H. J., Kang, E., Lee, S. Y., Kim, N. J., Yi, J., Park, W. B., & Oh, M. (2021). Antibody Responses 8 Months after Asymptomatic or Mild SARS-CoV-2 Infection. Emerging Infectious Diseases, 27(3), 928–931. https://doi.org/10.3201/eid2703.204543
Cosma, S., Carosso, A. R., Corcione, S., Cusato, J., Borella, F., Antonucci, M., Marozio, L., Revelli, A., Preti, M., Ghisetti, V., Di Perri, G., & Benedetto, C. (2021). Longitudinal analysis of antibody response following SARS-CoV-2 infection in pregnancy: From the first trimester to delivery. Journal of Reproductive Immunology, 144, 103285. https://doi.org/10.1016/j.jri.2021.103285
Darif, D., Hammi, I., Kihel, A., El Idrissi Saik, I., Guessous, F., & Akarid, K. (2021). The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microbial Pathogenesis, 153, 104799. https://doi.org/10.1016/j.micpath.2021.104799
Edlow, A. G., Li, J. Z., Collier, A. Y., Atyeo, C., James, K. E., Boatin, A. A., Gray, K. J., Bordt, E. A., Shook, L. L., Yonker, L. M., Fasano, A., Diouf, K., Croul, N., Devane, S., Yockey, L. J., Lima, R., Shui, J., Matute, J. D., Lerou, P. H., … Alter, G. (2020). Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Network Open, 3(12), e2030455. https://doi.org/10.1001/jamanetworkopen.2020.30455
Favre, G., Pomar, L., Musso, D., & Baud, D. (2020). 2019-nCoV epidemic: What about pregnancies? The Lancet, 395(10224), e40. https://doi.org/10.1016/S0140-6736(20)30311-1
Fenizia, C., Biasin, M., Cetin, I., Vergani, P., Mileto, D., Spinillo, A., Gismondo, M. R., Perotti, F., Callegari, C., Mancon, A., Cammarata, S., Beretta, I., Nebuloni, M., Trabattoni, D., Clerici, M., & Savasi, V. (2020). Analysis of SARS-CoV-2 vertical transmission during pregnancy. Nature Communications, 11(1), 5128. https://doi.org/10.1038/s41467-020-18933-4
Ferrer-Oliveras, R., Mendoza, M., Capote, S., Pratcorona, L., Esteve-Valverde, E., Cabero-Roura, L., & Alijotas-Reig, J. (2021). Immunological and physiopathological approach of COVID-19 in pregnancy. Archives of Gynecology and Obstetrics, 304(1), 39–57. https://doi.org/10.1007/s00404-021-06061-3
Fu, Y., Cheng, Y., & Wu, Y. (2020). Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica, 35(3), 266–271. https://doi.org/10.1007/s12250-020-00207-4
He, Z., Fang, Y., Zuo, Q., Huang, X., Lei, Y., Ren, X., & Liu, D. (2021). Vertical transmission and kidney damage in newborns whose mothers had coronavirus disease 2019 during pregnancy. International Journal of Antimicrobial Agents, 57(2), 106260. https://doi.org/10.1016/j.ijantimicag.2020.106260
Huang, Y., Tu, M., Wang, S., Chen, S., Zhou, W., Chen, D., Zhou, L., Wang, M., Zhao, Y., Zeng, W., Huang, Q., Xu, H., Liu, Z., & Guo, L. (2020). Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis. Travel Medicine and Infectious Disease, 36, 101606. https://doi.org/10.1016/j.tmaid.2020.101606
Li, M., Chen, L., Zhang, J., Xiong, C., & Li, X. (2020). The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLOS ONE, 15(4), e0230295. https://doi.org/10.1371/journal.pone.0230295
Lippi, G., & Plebani, M. (2020). Laboratory abnormalities in patients with COVID-2019 infection. Clinical Chemistry and Laboratory Medicine (CCLM), 58(7), 1131–1134. https://doi.org/10.1515/cclm-2020-0198
Liu, H., Wang, L.-L., Zhao, S.-J., Kwak-Kim, J., Mor, G., & Liao, A.-H. (2020). Why are pregnant women susceptible to COVID-19? An immunological viewpoint. Journal of Reproductive Immunology, 139, 103122. https://doi.org/10.1016/j.jri.2020.103122
Marot, S., Malet, I., Leducq, V., Zafilaza, K., Sterlin, D., Planas, D., Gothland, A., Jary, A., Dorgham, K., Bruel, T., Burrel, S., Boutolleau, D., Schwartz, O., Gorochov, G., Calvez, V., & Marcelin, A.-G. (2021). Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers. Nature Communications, 12(1), 1–7. https://doi.org/10.1038/s41467-021-21111-9
Melenotte, C., Silvin, A., Goubet, A.-G., Lahmar, I., Dubuisson, A., Zumla, A., Raoult, D., Merad, M., Gachot, B., Hénon, C., Solary, E., Fontenay, M., André, F., Maeurer, M., Ippolito, G., Piacentini, M., Wang, F.-S., Ginhoux, F., Marabelle, A., … Zitvogel, L. (2020). Immune responses during COVID-19 infection. OncoImmunology, 9(1), 1807836. https://doi.org/10.1080/2162402X.2020.1807836
Miesbach, W., & Makris, M. (2020). COVID-19: Coagulopathy, Risk of Thrombosis, and the Rationale for Anticoagulation. Clinical and Applied Thrombosis/Hemostasis, 26, 107602962093814. https://doi.org/10.1177/1076029620938149
Mor, G., Aldo, P., & Alvero, A. B. (2017). The unique immunological and microbial aspects of pregnancy. Nature Reviews Immunology, 17(8), 469–482. https://doi.org/10.1038/nri.2017.64
Mourad, M., Jacob, T., Sadovsky, E., Bejerano, S., Simone, G. S.-D., Bagalkot, T. R., Zucker, J., Yin, M. T., Chang, J. Y., Liu, L., Debelenko, L., Shawber, C. J., Firestein, M., Ouyang, Y., Gyamfi-Bannerman, C., Penn, A., Sorkin, A., Wapner, R., & Sadovsky, Y. (2021). Placental response to maternal SARS-CoV-2 infection. Scientific Reports, 11(1), 14390. https://doi.org/10.1038/s41598-021-93931-0
Nile, S. H., Nile, A., Qiu, J., Li, L., Jia, X., & Kai, G. (2020). COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine & Growth Factor Reviews, 53, 66–70. https://doi.org/10.1016/j.cytogfr.2020.05.002
Novoa, R. H., Quintana, W., Llancarí, P., Urbina-Quispe, K., Guevara-Ríos, E., & Ventura, W. (2021). Maternal clinical characteristics and perinatal outcomes among pregnant women with coronavirus disease 2019. A systematic review. Travel Medicine and Infectious Disease, 39, 101919. https://doi.org/10.1016/j.tmaid.2020.101919
Poon, L. C., Leung, B. W., Ma, T., Yu, F. N. Y., Kong, C. W., Lo, T. K., So, P. L., Leung, W. C., Shu, W., Cheung, K. W., Moungmaithong, S., & Wang, C. C. (2021). Relationship between viral load, infection‐to‐delivery interval and mother‐to‐child transfer of ANTI‐SARS‐COV ‐2 antibodies. Ultrasound in Obstetrics & Gynecology, 57(6), 974–978. https://doi.org/10.1002/uog.23639
Qeadan, F., Mensah, N. A., Tingey, B., & Stanford, J. B. (2021). The risk of clinical complications and death among pregnant women with COVID-19 in the Cerner COVID-19 cohort: A retrospective analysis. BMC Pregnancy and Childbirth, 21(1), 305. https://doi.org/10.1186/s12884-021-03772-y
Qiao, J. (2020). What are the risks of COVID-19 infection in pregnant women? The Lancet, 395(10226), 760–762. https://doi.org/10.1016/S0140-6736(20)30365-2
Rad, H. S., Röhl, J., Stylianou, N., Allenby, M. C., Bazaz, S. R., Warkiani, M. E., Guimaraes, F. S. F., Clifton, V. L., & Kulasinghe, A. (2021). The Effects of COVID-19 on the Placenta During Pregnancy. Frontiers in Immunology, 12, 743022. https://doi.org/10.3389/fimmu.2021.743022
Rahimzadeh, M., & Naderi, N. (2021). Toward an understanding of regulatory T cells in COVID‐19: A systematic review. Journal of Medical Virology, 93(7), 4167–4181. https://doi.org/10.1002/jmv.26891
Rangchaikul, P., & Venketaraman, V. (2021). SARS-CoV-2 and the Immune Response in Pregnancy with Delta Variant Considerations. Infectious Disease Reports, 13(4), 993–1008. https://doi.org/10.3390/idr13040091
Savirón-Cornudella, R., Villalba, A., Esteban, L. M., Tajada, M., Rodríguez-Solanilla, B., Andeyro-Garcia, M., Zapardiel, J., Rite, S., Castán-Larraz, B., & Pérez-López, F. R. (2021). Screening of severe acute respiratory syndrome coronavirus-2 infection during labor and delivery using polymerase chain reaction and immunoglobulin testing. Life Sciences, 271, 119200. https://doi.org/10.1016/j.lfs.2021.119200
Sherer, M. L., Lei, J., Creisher, P. S., Jang, M., Reddy, R., Voegtline, K., Olson, S., Littlefield, K., Park, H.-S., Ursin, R. L., Ganesan, A., Boyer, T., Elsayed, N., Brown, D. M., Walch, S. N., Antar, A. A. R., Manabe, Y. C., Jones-Beatty, K., Golden, W. C., … Burd, I. (2021). Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection. American Journal of Obstetrics and Gynecology, 225(3), 301.e1-301.e14. https://doi.org/10.1016/j.ajog.2021.03.028
Taglauer, E. S., Wachman, E. M., Juttukonda, L., Klouda, T., Kim, J., Wang, Q., Ishiyama, A., Hackam, D. J., Yuan, K., & Jia, H. (2022). Acute Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy Is Associated with Placental Angiotensin-Converting Enzyme 2 Shedding. The American Journal of Pathology, S0002944022000116. https://doi.org/10.1016/j.ajpath.2021.12.011
Wastnedge, E. A. N., Reynolds, R. M., van Boeckel, S. R., Stock, S. J., Denison, F. C., Maybin, J. A., & Critchley, H. O. D. (2021). Pregnancy and COVID-19. Physiological Reviews, 101(1), 303–318. https://doi.org/10.1152/physrev.00024.2020
Xu, H., Zhong, L., Deng, J., Peng, J., Dan, H., Zeng, X., Li, T., & Chen, Q. (2020). High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. International Journal of Oral Science, 12(1), 1–5. https://doi.org/10.1038/s41368-020-0074-x
Zhang, H., & Zhang, H. (2021). Entry, egress and vertical transmission of SARS-CoV-2. Journal of Molecular Cell Biology, 13(3), 168–174. https://doi.org/10.1093/jmcb/mjab013
Zhong, Y., Cao, Y., Zhong, X., Peng, Z., Jiang, S., Tang, T., Chen, H., Li, X., Xia, Y., Cheng, Y., & Zhao, X. (2021). Immunity and coagulation and fibrinolytic processes may reduce the risk of severe illness in pregnant women with coronavirus disease 2019. American Journal of Obstetrics and Gynecology, 224(4), 393.e1-393.e25. https://doi.org/10.1016/j.ajog.2020.10.032
Zhou, J., Wang, Y., Zhao, J., Gu, L., Yang, C., Wang, J., Zhang, H., Tian, Y., Tuo, H., Li, D., Wei, M., & He, B. (2021). The metabolic and immunological characteristics of pregnant women with COVID-19 and their neonates. European Journal of Clinical Microbiology & Infectious Diseases, 40(3), 565–574. https://doi.org/10.1007/s10096-020-04033-0
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Copyright (c) 2022 José Jefferson da Silva Cavalcanti Lins; Gabriel Soares de Souza; Estela Maria Dantas de Morais ; Placido de Carvalho Silva Neto; Jurandy Júnior Ferraz de Magalhães; Valda Lúcia Moreira Luna; Carolina Maria da Silva; Pauliana Valéria Machado Galvão; George Alessandro Maranhão Conrado
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