Is There a ‘Preeclampsia-Like’ Syndrome in Pregnant Women with COVID-19?

PURPOSE:

  • There is overlapping symptomatology between preeclampsia (PE) and COVID-19 including liver injury and coagulopathy
    • Being able to differentiate between the two could have significant implications for clinical care as PE with severe features usually requires delivery
  • Mendoza et al. (BJOG, 2020) sought to investigate pregnancies with COVID-19 and determine, based on clinical, ultrasound and biochemical findings if patients with true PE vs ‘PE-like’ features could be distinguished

METHODS:

  • Prospective observational study
    • Tertiary referral hospital
  • Participants
    • Singleton pregnancies
    • Confirmed or suspected COVID-19
    • >20w0d gestation
  • Classified in to two groups: Severe vs nonsevere COVID-19, based on presence of severe pneumonia
  • Aside from clinical outcomes, the following ultrasound and biochemical parameters were also assessed in patients with suspected PE
    • Uterine artery pulsatility index (UtAPI)
    • Angiogenic factors: Soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF)
  • Primary outcome measures
    • Incidence of signs and symptoms related to PE, including
      • Hypertension | Proteinuria | Thrombocytopenia | Elevated liver enzymes | Abnormal UtAPI and increased sFlt-1/PlGF
    • “UtAPI >95th centile for gestational age, and sFlt-1/PlGF values ≥85 (at <34 weeks) or ≥110 (at ≥34 weeks) were considered highly suggestive of underlying placental disease”

RESULTS:

  • 42 consecutive pregnancies were recruited
    • Nonsevere: 34
    • Severe (requiring ICU admission): 8
  • Clinical course of severe group
    • Prior to onset of severe pneumonia, all 8 women were normotensive and only 1 patient had elevated UtAPI
  • Median age of severe cases (39.4 years) were significantly higher than nonsevere (30.9 years); p=0.006
  • Following severe pneumonia onset, 6 women (14.3% of total cohort) met PE criteria including
    • New onset hypertension and proteinuria and/or thrombocytopenia and/or elevated liver enzymes
    • No cases met diagnostic criteria in the nonsevere group
    • All required antihypertensive medication
    • Only 1 patient had abnormal LDH level >600 UI/L, sFlt-1/PlGF, and UtAPI
    • 4 cesarean births
      • HELLP syndrome (1 case)
      • Worsening COVID-19 (3 cases)
  • Two cases were still pregnant after recovery from severe pneumonia
    • PE-like syndrome resolved in both cases

CONCLUSION:

  • Pregnant women with severe COVID-19 can develop a PE-like syndrome
  • The authors suggest that only 1 out of the 8 cases demonstrated ultrasound and biochemical features compatible with placental dysfunction
    • PE-like syndrome vs PE could possibly be differentiated based on these biochemical markers (sFlt-1/PlGF, LDH) and Doppler (UtAPI) features
  • Based on the resolution in 2 of the cases, the authors state that

PE-like syndrome might not be an indication for earlier delivery in itself since it might not be a placental complication and could resolve spontaneously after recovery from severe pneumonia.

Learn More – Primary Sources:

Preeclampsia-like Syndrome Induced by Severe COVID-19: A Prospective Observational Study

Commentary: Can COVID‐19 in pregnancy cause preeclampsia?

FDA Revokes Hydroxychloroquine and Chloroquine EUA for the Treatment of COVID-19

SUMMARY:

The FDA has revoked the Emergency Use Authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate. Based on the available data, these medications do not appear to be effective in the treatment of COVID-19 and also present harms, specifically related to cardiac arrhythmias.

  • An EUA is different than a full FDA approval
    • EUA based on an FDA evaluation of evidence and risks vs potential or known benefits of “unproven” products during an emergency
  • Chloroquine phosphate and hydroxychloroquine sulfate, donated to the Strategic National Stockpile, received an EUA to be used to treat certain hospitalized patients with COVID-19 when a clinical trial was unavailable, or participation in a clinical trial was not feasible
  • Based on benefits/harms analysis, these medications no longer meet the EUA requirements

KEY POINTS:

  • Research has demonstrated the following regarding hydroxychloroquine and chloroquine (see ‘Related ObG Entries’ below)
    • Hydroxychloroquine showed no benefit on mortality or in speeding recovery (RCT)
    • Suggested dosing regimens for chloroquine and hydroxychloroquine are unlikely to kill or inhibit the virus that causes COVID-19
    • “The totality of scientific evidence currently available indicate a lack of benefit”
  • FDA approved use of chloroquine and hydroxychloroquine
    • Still both FDA-approved to treat or prevent malaria
    • Hydroxychloroquine is also approved to treat autoimmune conditions such as chronic discoid lupus erythematosus, systemic lupus erythematosus in adults, and rheumatoid arthritis

Note: “FDA approved products may be prescribed by physicians for off-label uses if they determine it is appropriate for treating their patients, including during COVID”

Possible Drug Interaction with Remdesivir

  • The FDA also released a warning regarding a potential drug interaction between remdesivir and chloroquine and hydroxychloroquine
  • Data derived from a non-clinical laboratory study demonstrated possible reduction in the antiviral activity of remdesivir activity when co-administered with these medications
  • The FDA is not currently aware of reduced activity in the clinical setting and continues to evaluate data on this subject

Learn More – Primary Sources:

Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine

Coronavirus (COVID-19) Update: FDA Warns of Newly Discovered Potential Drug Interaction That May Reduce Effectiveness of a COVID-19 Treatment Authorized for Emergency Use