Immunological aspects of coronavirus disease during pregnancy: an integrative review

Silva, Camila Radelley Azevedo Costa da; Oliveira, Lisiane Vital de; Lopes, Lorenna Peixoto; Santos, Wancler Albert Gomes dos; Agra, Isabela Karine Rodrigues

doi:10.1590/1806-9282.66.5.696

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Revista da Associação Médica Brasileira

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REVIEW ARTICLE • Rev. Assoc. Med. Bras. 66 (5) • May 2020 • https://doi.org/10.1590/1806-9282.66.5.696 copy

Immunological aspects of coronavirus disease during pregnancy: an integrative review

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE

To review the immunological aspects of the 2019 coronavirus disease (COVID-19) in pregnancy, based on the scientific evidence currently available.

METHODS

An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed) and LILACS databases, using the descriptors “pregnancy” and “COVID-19”. This search included articles published up until 14th April 2020 published in English, Spanish or Portuguese. After reading the articles available in their entirety, those related specifically to the immunological aspects of the disease in pregnancy were selected. We initially found a total of 62 articles; 52 were accessed in full-text, and 5 were finally selected.

RESULTS

Pregnant women are more affected by respiratory diseases possibly because of physiological, immune, and anatomical changes. Some studies highlight the important shift to a T-helper lymphocyte type 2 (Th2) immune response in pregnancy, as a potential contributor to the severity in cases of COVID-19. Additionally, the cytokine storm present in severe cases leads to an increased inflammatory state, which may deteriorate the clinical prognosis in this population. Therefore, pregnant women may represent a vulnerable group to COVID-19 infection, primarily due to the immune imbalance in the maternal-fetal interface.

CONCLUSION

Maternal immune response probably plays an important role in the pathophysiology of this infection, although some details remain unsolved. Although further studies are needed to deeply investigate the immunological aspects of the disease in pregnancy, our findings may provide insights into the possible immune mechanisms involved in the pathophysiology of COVID-19 in pregnancy.

Pregnancy; Immunity; COVID-19; Coronavirus infections; Pandemics

Author, Year	Study Design	Main Results
Dashraath et al.⁸ 2020	Narrative Review	Pregnant women are known to be more affected by respiratory illness, which is associated with increased morbidity and mortality rates. In pregnancy, the physiological shift to a Th2 dominant environment contributes to overall infections by increasing maternal susceptibility to intracellular pathogens like viruses. Patients with SARS showed preferential activation of lymphocyte T-helper type 1 (pro-inflammatory) response. Authors postulated that transition to a lymphocyte T-helper type 2 environment in pregnancy, favoring the expression of anti-inflammatory cytokines, may result in milder cases of COVID-19 in pregnancy.
Chen et al.¹³ 2020	Narrative Review	Pregnant women are more susceptible to the virus due to immune and anatomic alteration. Alterations in cellular immunity, such as down-regulation of lymphocyte proliferation and activation, are primarily aimed at adopting maternal immune tolerance to the fetus. Despite the limited sample sizes of the studies analyzed, the authors suggest a higher fatality rate in the pregnant population.
Liu et al.¹⁴ 2020	Narrative Review	Pregnant women represent a uniquely vulnerable group in any infectious disease outbreak due to their altered physiology, compromised mechanical and immunological functions. The COVID-19 infection is associated with a cytokine-storm, which leads to an important increase of inflammatory mediators at the maternal-fetal interface. As a result, pregnant women may face severe morbidity and mortality.
Jiao¹⁵ 2020	Narrative Review	Update on the issues that may be faced by different groups of pregnant populations: late, middle, and early pregnancy, as the maternal immune response varies during the different stages of pregnancy. In early pregnancy, the immune system is very sensitive and unstable, favoring more severe infections and serious immune fetal and maternal disorders. The author recommended first and second-trimester follow-ups to anticipate those risks.
Ashokka et al.¹⁶ 2020	Narrative Review	Given the limited knowledge about this novel coronavirus, which has both similarities and differences to SARS-CoV-1 and MERS-CoV, the authors provided a general guide based upon currently available evidence. They also postulated that cytokine-storm, leading to an increase in levels of inflammatory mediators, is associated with disease severity and admission in ICU.

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[1] CORRESPONDING AUTHOR: Isabela Karine Rodrigues Agra Faculdade de Medicina da Universidade Federal de Alagoas (UFAL) - Campus A. C. Simões Av. Lourival Melo Mota s/n, Tabuleiro dos Martins, Maceió, AL, Brasil - 57072-900 Tel: +55 82 3214-1858 E-mail: agraisabela@gmail.com