Congenital Zika syndrome: is the heart part of its spectrum?

Santana, Monique Barreto; Lamas, Cristiane da Cruz; Athayde, Jonathan; Calvet, Guilherme Amaral; Moreira, João; Lorenzo, Armando

doi:10.1016/j.cmi.2019.03.020

Cited by 18 publications

(21 citation statements)

References 4 publications

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“…Dose response. Halai et al (2017) 120 examined the severity of congenital outcomes according to measures of the severity of maternal ZIKV infection in a subset of mothers in the cohort presented by Brasil et al (2016) 274 . They evaluated ZIKV load, assessed by RT-PCR using the cycle threshold (CT) as a measure of number of RNA copies, and a severity score of symptoms in 131 pregnant women.…”

Section: Resultsmentioning

confidence: 99%

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Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

et al. 2019

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Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I2=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I2=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I2=0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I2=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I2=74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.

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Section: Resultsmentioning

confidence: 99%

“…During this review period, we included 17 case reports 46, 220– 235 , 22 case series 120, 236– 256 , seven case-control studies 4, 257– 262 , one ecological study 266 , one modelling study 265 and eight outbreak reports 201, 203, 206, 266– 270 that reported on ZIKV infection and GBS.…”

Section: Resultsmentioning

confidence: 99%

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

et al. 2019

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“…Congenital cardiovascular anomalies were identified in children exposed to ZIKV such as cardiomyopathy, hyperechogenicity of aortic valve, mitral valve, and aortic root [19,58,64,100]. Other studies have also described cardiological symptoms and imaging findings such as complex congenital heart disease, echocardiographic abnormalities, and cardiac overload [148][149][150][151].…”

Section: Plos Onementioning

confidence: 99%

Congenital Zika syndrome: A systematic review

et al. 2020

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Background The signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome. Methods and findings A systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age. Conclusions Zika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols.

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“…In early 2018, an infant was born with congenital heart defects to a mother with a confirmed case of ZIKV infection, and the child presented with hypoplastic left heart syndrome and other features of CZS including microcephaly [7]. Subsequently, three large studies reported increases in the occurrence of cardiac defects in infants with CZS [8][9][10]. For example, Noronha et al assessed heart pathology and reported minor cardiac pathology in two out of the five cases, but markers of ZIKV infection were not detected in the heart tissue [11].…”

Section: Introductionmentioning

confidence: 99%

Characterization of zika virus infection of human fetal cardiac mesenchymal stromal cells

et al. 2020

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Zika virus (ZIKV) is a single-stranded RNA virus belonging to the family Flaviviridae. ZIKV predominantly enters cells using the TAM-family protein tyrosine kinase receptor AXL, which is expressed on a range of cell types, including neural progenitor cells, keratinocytes, dendritic cells, and osteoblasts. ZIKV infections have been associated with fetal brain damage, which prompted the World Health Organization to declare a public health emergency in 2016. ZIKV infection has also been linked to birth defects in other organs. Several studies have reported congenital heart defects (CHD) in ZIKV infected infants and cardiovascular complications in adults infected with ZIKV. To develop a better understanding of potential causes for these pathologies at a cellular level, we characterized ZIKV infection of human fetal cardiac mesenchymal stromal cells (fcMSCs), a cell type that is known to contribute to both embryological development as well as adult cardiac physiology. Total RNA, supernatants, and/or cells were collected at various time points post-infection to evaluate ZIKV replication, cell death, and antiviral responses. We found that ZIKV productively infected fcMSCs with peak (~70%) viral mRNA detected at 48 h. Use of an antibody blocking the AXL receptor decreased ZIKV infection (by~50%), indicating that the receptor is responsible to a large extent for viral entry into the cell. ZIKV also altered protein expression of several mesenchymal cell markers, which suggests that ZIKV could affect fcMSCs' differentiation process. Gene expression analysis of fcMSCs exposed to ZIKV at 6, 12, and 24 h post-infection revealed up-regulation of genes/pathways associated with interferonstimulated antiviral responses. Stimulation of TLR3 (using poly I:C) or TLR7 (using Imiquimod) prior to ZIKV infection suppressed viral replication in a dose-dependent manner. Overall, fcMSCs can be a target for ZIKV infection, potentially resulting in CHD during embryological development and/or cardiovascular issues in ZIKV infected adults.

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Congenital Zika syndrome: is the heart part of its spectrum?

Cited by 18 publications

References 4 publications

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

Congenital Zika syndrome: A systematic review

Characterization of zika virus infection of human fetal cardiac mesenchymal stromal cells

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