COVID-19 Update #3: Treating the Pregnant Patient

Prevention of COVID-19: More Updates on Vaccination

  • Vaccination is the #1 thing folks can do to protect themselves and their fetuses!

  • Since our last podcast, ACOG, SMFM, ASRM, ACNM, AABM (just to name a few) have all endorsed COVID-19 vaccination at any time for folks trying to conceive, who are pregnant, or postpartum and lactating!

  • SMFM has released consensus guidance for healthcare providers regarding vaccine counseling:

    • Check out our previous episodes (#1 and #2) on vaccine effectiveness

    • We at CREOGs Over Coffee wholeheartedly recommend vaccination, especially with this stronger data regarding safety in reproduction, pregnancy, and lactation.

COVID and Pregnancy: What Options Are Available for Treatment?

We’re going to address the following major questions today:

  • Does patient merit inpatient admission?

  • If they can stay outpatient, does the patient qualify for any therapy?

  • If they need to be inpatient, when to start therapeutics and what options are available? 

  • When is delivery indicated for maternal benefit?

Decision to Admit:

COVID can be broken into asymptomatic disease, then mild, moderate, severe, and critical disease:

  • Mild

    • Flu-like symptoms: fever, cough, myalgias

    • Anosmia

    • No dyspnea, shortness of breath, or abnormal chest imaging (if performed)

  • Moderate:

    • Symptomatic dyspnea/shortness of breath, but able to maintain SpO2 > 94% on room air

    • Evidence of pneumonia on imaging

    • Refractory fever (>39C) to acetaminophen

  • Severe:

    • Respiratory rate > 30

    • SpO2 < 94% on room air (so any O2 requirement!)

    • PaO2 / FiO2 < 300 

    • More than 50% lung area involvement of disease on imaging

  • Critical:

    • Multiorgan failure or dysfunction, shock

    • Respiratory failure requiring high flow nasal cannula or mechanical ventilation

  • Patients with mild disease or no symptoms can be safely monitored outpatient, with a 10-day self quarantine from positive test or onset of symptoms in accordance with CDC guidelines. 

  • Patients with moderate disease will often require hospitalization in pregnancy, owing to risk of progression. However, this is an individualized decision, and non-pregnant folks might more typically stay outpatient in this scenario.

    • If patients remain outpatient, SMFM recommends ongoing check-ins from patients to their prenatal care providers to assess symptoms and ensure there is no concern for disease progression.

    • Also recommend a follow up visit (either in-person or via telemedicine) at least once within 2 weeks of diagnosis.

    • Necessary and indicated medical care should not be avoided due to a positive COVID status!

  • Patients with severe or critical disease, obviously, will merit inpatient admission. 

  • Patients with mild-moderate disease with other comorbidities may also be considered for hospitalization (i.e., patients with hypertension, diabetes, other maternal medical conditions), as these patients appear to be more prone to acute decompensation. 

Inpatient Care: Protocols and Hospital Disposition

  • Vital signs and fetal monitoring as indicated when fetal intervention would be considered.

  • ICU level of care should be considered with:

    • Rapidly increasing oxygen needs to maintain SpO2 >95%

    • Hypotension (MAP < 65) despite some measure of fluid resuscitation.

      • Owing to risk of pulmonary edema, SMFM recommends an initial 500-1000cc bolus of crystalloid to assess response, and conservative fluid management unless clearly hypovolemic.

    • Need for mechanical ventilation or intubation - 

      • Intubation is recommended if O2 requirements are >15L by NC or mask, >40-50L by high-flow NC, >60% FiO2 by Venturi mask, or altered mental status with inability to protect airway. 

    • Need for other end-organ support (i.e., hemodialysis)

  • Prone positioning is possible in pregnancy! 

    • Proning in COVID (and other causes of acute respiratory distress syndrome) is well-studied

      • It is hypothesized to decrease ventilation-perfusion mismatch by bringing more blood to the more open anterior lung fields (rather than the often atelectasis-affected lower posterior lung).

    • Padding and support devices may need to be used for appropriate support in pregnancy.

    • In non-intubated patients, lateral-decubitus or full-prone positioning is also permissible and can help improve oxygenation.

  • Thromboprophylaxis is generally recommended in at least hospitalized patients, given critical illness increases hypercoagulability risk further in pregnancy.

    • Prophylaxis is generally not recommended after discharge, unless other specific comorbidities exist.

      • SMFM offers use of a risk scale, the IMPROVE Risk Score, as well as deferring to clinical expertise to guide use of pharmacologic prophylaxis once discharged from the hospital.

  • Extracorporeal membrane oxygenation (ECMO)

    • Allows for oxygenation of the lungs (VV ecmo) and possibly combining with pumping action (VA ecmo) in patients with severe ARDS refractory to other methods of therapy. 

      • It gets even more complicated than this, but that’s the basics!

    • ECMO is a significant intervention with its own set of morbidities and risks, and should be reserved for significant, severe cases of pregnancy where it may be helpful and delivery may not/cannot be considered at that present moment (i.e., previable or periviable gestation). 

    • These conversations are often very individualized by institution, so we’ll hold off on further discussion from here! 


Therapeutics and Indications

  • Outpatient:

    • Monoclonal antibody therapy (i.e., Regeneron)

      • FDA Emergency Use Authorization indicated for patients over age 12 who have mild-to-moderate COVID-19, weigh at least 40kg, and are at high risk of progression to severe disease or hospitalization. The criteria are:

        • BMI > 35

        • Chronic kidney disease

        • Diabetes

        • Immunosuppresive therapy 

      • Data is limited on their use in pregnancy, but other monoclonal antibodies are generally well-tolerated with no fetal effects. Thus, they can be used in appropriate pregnant patients. 

  • Inpatient:

    • Dexamethasone

      • Associated with decreased risk of mortality in those requiring mechanical ventilation

      • Also has small decrease in mortality for those requiring oxygen generally

        • (RECOVERY Trial)

      • Recommended dosing: 6mg IV or PO daily x 10 days.

        • NOT recommended in those who do not require oxygen

      • Dexamethasone does cross the placenta measurably: it is the alternative steroid to betamethasone for fetal lung maturity!

        • FLM dosing: 6mg IM q12h x 4 doses

        • Thus, it is appropriate to use in appropriate pregnant patients; FLM dosing should be given for the first 48h of therapy. 

    • Remdesivir

      • Associated with decreased duration of disease in patients requiring oxygen therapy (ACTT-1 Trial)

      • Recommended if SpO2 < 94% on mechanical ventilation or ECMO

      • No fetal toxicity is known, and can be used on an emergency / compassionate use basis.

When to deliver the hospitalized patient:

  • SMFM recommends that in patients with refractory hypoxemia, delivery at/after 32 weeks is reasonable if it will allow for further care optimization given:

    • Low risk of neonatal mortality at 32 weeks (0.2%) and

    • Overall low risk of major morbidity (8.7% at 32 weeks). 

      • This also logistically is often more appropriate - controlled delivery is certainly more preferable to chaos! 

  • In those who are critically ill, decision for delivery is certainly individualized.

    • Mechanical ventilation alone is not an indication for delivery.

    • Proning, ECMO, and other ventilator methods should be considered especially under 30-32 weeks. 

COVID-19 Updates for Pregnancy

Since our update in March, we now have much more data – so much in fact that it may be really hard for everyone to synthesize it all. Our hope is to help a little with the synthesis and present the information out there in a digestible way – obviously we won’t be totally comprehensive, but we’ll do our best!

Pregnancy and COVID-19 Risk

The CDC released a new morbidity and mortality weekly report (MMWR) in November 2020:

  • Looked at data from 1/22-10/3/2020 with delay for data updates up to 10/28/2020 in both pregnant and nonpregnant symptomatic women between the ages of 15-44 (reproductive age).

    • 409,462 symptomatic women 

    • 23,434 (5.76%) symptomatic pregnant women 

  • Suggestion: pregnant women are MORE likely to have severe COVID-19 associated illness. After adjusting for age, race, other med conditions, pregnancy women were: 

    • More likely to be admitted to the ICU (10.5 vs 3.9/1000 cases, ARR 3.0) 

    • More likely to receive ventilation (2.9 vs 1.1/1000, ARR 2.9) 

    • Receive ECMO (0.7 vs 0.3/1000, ARR 2.4) 

    • And die… (1.5 vs 1.2/1000, ARR 1.7) 

  • Some other interesting findings: 

    • Older pregnant women were more likely to have ICU admission/severe disease, comparing women 35-44 with women 15-24 (19.4 vs 7.6/1000 cases) 

    • Black women had higher risk of death (made up of 14.1% of all women involved, but represented 36.6% of deaths overall, including 26.5% of pregnancy deaths) 

    • Increased risk of ICU admission for Asian women (ARR 6.6) and native Hawaiian/Pacific Island women (ARR 3.7) 

    • In pregnant Hispanic women, pregnancy was associated with 2.4x risk of death 

  •     Some limitations: 

    • COVID-19 cases rely on voluntary report by health care providers and public health officials/agencies 

    • Reporting bias – we might report more if there is more severe disease (less likely to report asymptomatic or mild disease) 

    • Severe outcomes might require more time to ascertain (why they had time lag of 10/28 when looking at cases reported through 10/3/2020).

Smaller studies have been performed to assess other pregnancy outcomes. Studies may be too small to be powered for these differences, but are still being actively studied:

  • Preterm labor/stillbirth 

    • Overall during the pandemic:

      • Danish report showed decreased preterm birth rates overall;

      • Another UK study showed increased rates of both;,

      • JAMA Dec 7, 2020 in Philadelphia did not show increased rate during the pandemic. But conflictingly, a study in the same city in October showed that there was a decreased PTB rate at one hospital 

      • Could hypothesize these varying outcomes may be due to different time periods, different lock-down methods, etc. 

  • PEC/cesarean deliveries/PTB in people with COVID 

    • One study from Texas looked at 3374 women who were tested for COVID, of whom 252 were positive.

    • In positive women, there was no difference in composite outcome of PEC w/ SF, cesarean delivery, or PTB.

  • Looking at PTB from the Birth and Neonatal Outcome MMRC from CDC: there was a preterm birth rate of 12.9% in women with COVID-19 infection, which was higher than general population in 2019 (10.2%), so maybe there is an increased risk for preterm delivery.

Birth and Neonatal Outcomes after COVID-19 

There has been concern about perinatal infection in women who are COVID-19 positive and laboring. Fortunately we’ve got some reassuring data on this front from the CDC:

  • 5252 women with lab-confirmed COVID-19’s babies  610 (21.3%) of infants had reported COVID results

    • Perinatal infection – uncommon (16, 2.6%) and occurred primarily among infants whose mother had COVID ID’ed within 1 week of delivery.

    • 8 of the infants were born preterm (26-35 weeks) and admitted to NICU 

    • 8 term infants who were positive, one was admitted to NICU for fever and O2, the others were not admitted, and one did not have info.

COVID-19 Vaccination in Pregnant and Breastfeeding People  

When we recorded the episode, we spoke primarily about the Pfizer vaccine. This information should apply in broad strokes the the Moderna vaccine as well, now that it has received approval as the 2nd mRNA vaccine.

  • mRNA vaccine – What is it, how does it work? 

    • mRNA: messenger RNA. It is single-stranded RNA molecule that is complementary to one of the DNA strands of a gene. Reaching back to med school: mRNA leaves the cell nucleus and moves to the cytoplasm where they code for different protein synthesis. Ribosome will move along the mRNA, read the base sequence, and use the genetic code to translate three-base triplet (codon) into its corresponding amino acid 

    • tRNA: which is attached to an amino acid, will match with mRNA to generate a sequence of amino acids to make up a protein 

  • The COVID-19 mRNA vaccine gives instructions to our cells to create a “spike protein,” which is a harmless piece of protein that is found on the surface of the virus that causes COVID-19 

  • Once the mRNA is used, the cell gets rid of the material… so you can’t get infected with COVID-19. It also doesn’t get encoded into our DNA!

    • Once your cell makes the protein, it presents it on the surface of the cell. The immune system will recognize that this protein doesn’t belong there and begin to build up an immune response and make antibodies, kind of like what would happen in the natural infection against COVID-19. 

    • At the end of the process, your immune system will recognize these surface proteins from COVID-19 and have the ability to fight them off, so if you come into contact with COVID-19, your immune system will be ready 

  • How was it developed so fast? 

    • Most of the time, vaccine trials take a long time because there are hang-ups in things that have nothing to do with science: funding, IRBs approval, etc.

    • But because this was coronavirus, there was a lot of funding and momentum from Operation Warp Speed.

    • Pfizer received $1.95 billion in July for production of 100 million doses of vaccine, and Congress directed almost $10 billion to the overall effort of vaccine development/distribution. Most of the time, vaccine research does not get this much money all at once! 

  • Is it safe?

    • For the Pfizer vaccine, the Phase 3 clinical trial began on July 27 and enrolled 43,661 participants, and 41,135 received a second dose

    • The trial concluded 11/13/2020, so there is at least 3.5 months’ worth of data. We don’t really expect long term outcomes to be different… since mRNA gets destroyed by the body so quickly.

    • Findings: 

      • Looking at 28 days after first dose of vaccine (remember, we need time for the vaccine to work), there were 170 confirmed cases of COVID-19: 162 in the placebo group vs. 8 in the vaccine group.

      • Efficacy was consistent across age, gender, race, and ethnicity demographics.

      • Efficacy was 95% overall, and 94% in adults >65 years of age.

      • Safety in general: well tolerated across all populations, no serious safety concerns observed. The only Grade 3 adverse event >2% in frequency was fatigue (3.8%) and headache (2.0%). Older adults tended to report fewer and milder solicited adverse effects following vaccination 

    •  What about reports of the 6 people that died in the Pfizer Phase III trial? 

      • 6 people did die in the trial. 4 were in the placebo arm, and 2 were in the actual vaccine arm.

        • Of the two that died: 1 was reported to have serious adverse event related to arteriosclerosis and died 3 days after dose 1; the other had a cardiac arrest 60 days after dose 2 and died 3 days later. Both were > 55 years of age. 

        • Of the 4 that died in placebo arm: 1 died 8 days after dose 1 with unknown event, one died of hemorrhagic stroke 15 days after dose 2, one died 34 days after dose 2 (unknown event), one died of MI 16 days after dose 1. 

    • Other serious adverse events 

      • The non-fatal SAE was 0.6% in the vaccine group and 0.% in the placebo group 

      • Vaccine group had higher rates of appendicitis (0.04%), acute MI (0.02%), and CVA (0.02%)

      • Placebo arm had higher rates of pneumonia (0.03%), afib (0.02%), and syncope (0.02%) 

    • Editorializing here: but the overall small numbers, the variety of things that occurred, and the lack of biologic plausibility in these SAEs suggest these likely happened by chance.

  • Should pregnant and breastfeeding people get vaccinated? 

    • Unfortunately, pregnant and breastfeeding people were excluded from the study 

    • Currently, the FDA has not excluded pregnant and breastfeeding people from getting the vaccine 

    • SMFM is in agreement – recommend that pregnant and lactating people have access to the vaccine 

    • Can engage in discussion about potential benefits and unknown risks with their providers 

COVID-19 for the OB/GYN

Today’s episode is an audio summary of the CDC and SMFM guidelines for COVID-19, focusing on the virus, identification, containment, and considerations for pregnancy and postpartum care. We do not explore treatments or any intricacies in either outpatient or inpatient care.

Rather than posting those guidelines here verbatim, we have gone through and identified a lot of reputable sources with factual, up-to-date information for healthcare providers:

We also mention in the episode a registry being established for pregnant patients with COVID-19. Please listen to learn more about how you can be involved.