High viral SARS-CoV-2 load in placenta of patients with hypertensive disorders after COVID-19 during pregnancy

  1. M Fabre
  2. P Calvo
  3. S Ruiz-Martinez
  4. M Peran
  5. D Oros
  6. A Medel Martinez
  7. M Strunk
  8. R Benito
  9. J Schoorlemmer
  10. C Paules

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Abstract

Introduction

Studies described an increased frequency of hypertensive disorders of pregnancy after a COVID-19 episode. There is limited evidence about SARS-CoV-2 viral load in placenta. This study aimed to investigate the relationship between SARS-CoV-2 viral load in placenta and clinical development of HDP after COVID-19 throughout different periods of gestation.

Methods

This was a case-control study in women with and without gestational hypertensive disorders (HDP) after SARS-CoV-2 infection diagnosed by RT-PCR during pregnancy. Patients were matched by gestational age at the moment of COVID-19 diagnosis. We performed an analysis of SARS-CoV-2 RNA levels in placenta.

Results

A total of 28 women were enrolled. Sixteen patients were diagnosed with COVID-19 during the third trimester and the remaining twelve patients in the others trimesters. Ten placentas (35.7%) were positive for SARS-CoV-2, nine of them (90%) belonged to the HDP group versus one (10%) in control group (p=0.009). Those cases with the highest loads of viral RNA developed severe-preeclampsia.

Conclusion

The presence of SARS-CoV-2 was more frequent in placentas of patients with HDP after COVID-19. There seems to be a relationship between high viral load in the placenta and the development of hypertensive disorders. We found SARS-CoV-2 viral load in placenta after birth in mothers infected at the first half of pregnancy, but with negative nasopharyngeal RT-PCR at delivery. Our data suggest that SARS-CoV-2 infection during pregnancy could trigger gestational hypertensive disorders through placenta-related mechanisms.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.09.07.21261607: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: All patients provided written informed consent.
    IRB: The study was approved by the Research Ethics Committee of the Community of Aragon (C.I. PI21/155 and COL21/000) and all patients provided written informed consent.
    Sex as a biological variableWe conducted a case-control study in women diagnosed with COVID-19 during pregnancy with and without gestational hypertensive disorders.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We perform an analysis of SARS-CoV-2 RNA levels in placental tissue and SARS-CoV-2 antibodies in umbilical cord.
    SARS-CoV-2
    suggested: None
    The SARS-CoV-2 IgG assay is designed to detect IgG antibodies to the nucleocapsid protein of SARS-CoV-2. (IgG; SARS-CoV-2 IgG Assay, Abbott Laboratories Ireland, Dublin, Ireland) and IgM+IgA antibodies (IgM+IgA; COVID-19 VIRCLIA IgM+IgA, Vircell Microbiologists, Granada, Spain).
    detect IgG
    suggested: None
    SARS-CoV-2. (IgG; SARS-CoV-2 IgG Assay, Abbott Laboratories Ireland, Dublin, Ireland)
    suggested: None
    IgM+IgA antibodies (IgM+IgA; COVID-19 VIRCLIA IgM+IgA, Vircell Microbiologists, Granada, Spain)
    suggested: None
    Software and Algorithms
    SentencesResources
    The SARS-CoV-2 IgG assay is designed to detect IgG antibodies to the nucleocapsid protein of SARS-CoV-2. (IgG; SARS-CoV-2 IgG Assay, Abbott Laboratories Ireland, Dublin, Ireland) and IgM+IgA antibodies (IgM+IgA; COVID-19 VIRCLIA IgM+IgA, Vircell Microbiologists, Granada, Spain).
    Abbott Laboratories
    suggested: None
    Statistical analysis was performed using SPSS 22.0.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The main limitation of our study is the small sample size. Further studies with a large number of patients are required to confirm the association between high SARS-CoV-2 viral load in placenta tissue and the development of HDP. Moreover, our hospital’s protocols changed as the pandemic progressed. Therefore, different methodologies have been used for viral RNA detection. As not all tests proved to be equally sensitive and specific, the use of distinct tests may have caused a discrepancy with studies published previously [13, 16, 22]. In addition, we do not have sequencing data from nasopharyngeal maternal swabs available, but all pregnant women were diagnosed before the alpha (B.1.1.7 UK) variant and delta (B.1.617.2 India) were routinely detected in our area. A final limitation to address is the fact that for each placenta we tested only a single sample. As SARS-CoV2 is not necessarily homogenously present (or absent) throughout the placenta, the identification of samples as positive or negative should be interpreted in this context. Among the strengths of the study, we highlight the inclusion of women who tested positive for SARS-CoV-2 in each of the three trimesters of pregnancy. We demonstrate a higher viral load in placental tissue in the case group than in the control group and a higher frequency of infected placentas. Besides, as SARS-CoV-2 RT-PCR test carried out at the time of birth showed all mothers tested negative, we could rule out the possibility of acute mater...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.09.07.21261607v1 on medRxiv
  3. Version published to 10.1159/000520179