Immunological aspects of coronavirus disease during pregnancy: an integrative review

Abstract

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.

COVID-19 during pregnancy: an overview of maternal characteristics, clinical symptoms, maternal and neonatal outcomes of 10,996 cases described in 15 countries

“…The results of our review demonstrate that the maternal characteristics, clinical symptoms, maternal and neonatal outcomes of 10,996 cases of COVID-19 and pregnancy described in 15 different countries are not worse or different from the general population. We suggest that, differently from what was previously published [26], pregnant women are not more affected by the respiratory complications of COVID-19, compared with non-pregnant available data. We also suggest that the important gestational shift Th1--Th2 immune response [34], known as a potential contributor to the severity in cases of viral infections during pregnancy [28], are counter-regulated by the enhancedpregnancy-induced ACE2-Ang-(1-7) axis [39].…”

“…Although many previous reports of COVID-19 during pregnancy had suggested that the pregnancy can impact negatively on the clinical course of infection [23][24][25], potentially bringing more maternal and perinatal complications [25,26], the data compiled in this review might tell the opposite. It was clear from previous virus outbreaks during pregnancy, especially the 2009 H1N1 [27][28][29][30] and also SARS [23,31,32] and MERS [23,32,33] that pregnancy was detrimental in defining perinatal/neonatal and maternal outcomes, when comparing pregnant to nonpregnant population.…”

“…Conversely, we also suggest, that down-regulation of ACE2 receptors induced by SARS-CoV-2 cell entry might have been detrimental in subjects with pre-existing ACE2 deficiency associated with pregnancy. This association might explain the worse perinatal outcomes described in the literature [26,[43][44][45].…”

Problems with Early Systematic Reviews: The Case of Coronavirus Disease 2019 (COVID-19) in Pregnancy

“…Since December 2019 when the infection was first identified, more than 41,000 MEDLINEindexed papers have been published on COVID-19. Up to 31st July 2020, at least 29 systematic reviews on COVID-19 and pregnancy with varying conclusions have been published (Abdollahpour and Khadivzadeh 2020;Akhtar et al 2020;Ashraf et al 2020;Capobianco et al 2020;Della Gatta et al 2020;Deniz and Tezer 2020;Di Mascio et al 2020;Dubey et al 2020;Elshafeey et al 2020;Hessami et al 2020;Juan et al 2020;Kasraeian et al 2020;Kotlyar et al 2020;Lopes de Sousa et al 2020;Matar et al 2020;Melo and Araújo 2020;Muhidin et al 2020;Segars et al 2020;Silva et al 2020;Smith et al 2020;Thomas et al 2020a, b;Trippella et al 2020;Trocado et al 2020;Turan et al 2020;Walker et al 2020;Yang et al 2020;Yoon et al 2020;Zaigham and Andersson 2020). Factors which are likely to cause bias and thus, inaccuracy in subsequent analysis in systematic reviews were then identified and compiled.…”

Gestação e pandemia da COVID-19: Impactos no binômio materno-fetal

“…Essa população e seus conceptos são considerados de alto risco frente doenças infecciosas, já que alterações ocorridas no período gestatório exacerbam a sensibilidade geral para infecções. Do ponto de vista mecânico, à medida que a gravidez progride, adaptações corpóreas como a elevação do diafragma, a compressão da caixa torácica e volumes pulmonares alterados acabam por acarretar falta de ar e incapacidade de limpeza eficaz das secreções pulmonares, tornando esse grupo mais intolerante a hipóxia (Ribeiro et al, 2021;Silva et al, 2020;Tellau et al, 2020). Com o aumento do volume plasmático, do débito cardíaco e a diminuição da resistência vascular, ocorre um estado de dispneia fisiológica e alcalose respiratória, o que favorece a contaminação por patógenos respiratórios.…”