Guidance on COVID-19 Vaccine Including Pregnancy

SUMMARY: 

The CDC does not currently recommend COVID-19 vaccination during pregnancy and the lactation period in the absence of other risk factors. However, ACOG and SMFM continues to recommend vaccination during pregnancy and lactation to mitigate the significant risks associated with COVID. 

• Pregnancy Counseling Points
• Maternal and Obstetric Risk
• Considerations for Administration During Pregnancy
• Fetal Considerations
• CDC Adverse Event Data
• Breastfeeding
• Antibody Titers in Pregnancy

Pregnancy Counseling Points  

• Counseling should include the following elements 
  • Available data on vaccine safety 
  • Potential side effects (e.g., site pain, headache, fatigue, fever and rarely allergic reactions including anaphylaxis)
    • Risk of side effects not increased in pregnancy
  • Pregnant patients have higher risk of moderate to severe disease 
  • Level of COVID-19 community transmission 

Maternal and Obstetric Risk  

• With symptomatic COVID-19, pregnancy is an independent risk factor compared to symptomatic non-pregnant patients for 
  • ICU admission: 3-fold increase 
  • Mechanical ventilation 
  • ECMO: 2 to 4 fold increase 
  • Death: 1.7 fold increase 
  • May increase preterm birth and stillbirth 
• Other risk factors for severe COVID-19 disease include 
  • Cancer | Chronic kidney disease | COPD | Heart conditions | Immunocompromised state | Sickle cell disease | Smoking 
• Hispanic or Latinx and Black patients are disproportionally affected by higher prevalence of COVID-19 
  • More severe maternal morbidity | Higher risk of death 

Considerations for Administration During Pregnancy  

• Pregnancy test prior to vaccination is not recommended 
• No need to delay pregnancy following vaccine administration 
• No trimester-specific indications at this time 

Fetal Considerations 

• mRNA vaccines 
  • Available data suggests low risk 
  • Rapid degradation (approximately 10 to 20 days) 
  • Does not enter the cell’s nucleus or become integrated into the DNA; therefore, “no risk of genetic modification to people receiving the vaccine” 
• Maternal antibodies cross the placenta | May provide neonatal protection 

CDC Adverse Event Data    

• Healthcare providers are required to report certain adverse events following COVID-19 vaccination to the Vaccine Adverse Event Reporting System (VAERS)
• “Anyone can submit a report to VAERS – healthcare professionals, vaccine manufacturers, and the general public. VAERS welcomes all reports, regardless of seriousness, and regardless of how likely the vaccine may have been to have caused the adverse event.”

Breastfeeding  

• Vaccination is recommended during lactation
• Counseling should provide balance with respect to lack of data vs the patients’ individual risk for infection and severe disease 
• Although there is a lack of data “the theoretical risks regarding the safety of vaccinating lactating people do not outweigh the potential benefits of the vaccine” 

Antibody Titers in Pregnancy 

• Studies have demonstrated vaccine-induced antibody titers to be similar in pregnant women compared to nonpregnant women 
• Transfer of antibodies to newborns following maternal vaccination may confer neonatal protection 
  • Vaccine-induced IgG is transferred to the neonate 
  • Higher umbilical cord blood titers are associated with longer time intervals from vaccination 
  • Second vaccine dose increases cord blood IgG levels 

KEY POINTS: 

• The COVID-19 vaccine should be recommended to all pregnant and lactating patients 
• There is no preference for any particular approved vaccine
• Providers should discuss individual risks and benefits of the vaccine during pregnancy 
• Safety profile from the CDC Adverse Event Monitoring site shows no increased risk of worse pregnancy outcomes post-vaccination
• COVID-19 vaccines and other vaccines may be administered together (e.g., flu or Tdap)

Learn More – Primary Resources 

SMFM: Provider Considerations for Engaging in COVID-19 Vaccine Counseling With Pregnant and Lactating Patients 

SMFM: COVID_Vaccine

SMFM Reaffirms COVID-19 Vaccination Recommendations During Pregnancy

CDC: COVID-19 Vaccines 

ACOG Practice Advisory: COVID-19 Vaccination Considerations for Obstetric–Gynecologic Care 

CDC: Vaccine Adverse Event Reporting System (VAERS) 

mRNA-Based COVID-19 Vaccines Induce Robust, Persistent Immune Responses in Humans

BACKGROUND AND PURPOSE: 

• The mRNA-based COVID-19 vaccines are 95% effective at preventing COVID-19, but immune system dynamics induced by the vaccines are not clear 
• Turner et al. (Nature, 2021) examined antigen-specific B cell responses in peripheral blood and lymph nodes in individuals who received 2 doses of the Pfizer vaccine 

METHODS: 

• Observational study 
• Participants 
  • Healthy US adults who received both doses of Pfizer’s COVID-19 vaccine 
• Study design 
  • Blood samples were collected at baseline (before first dose), and at weeks 3 (pre-second dose), 4, 5, 7, and 15 
  • Fine needle aspirates of the draining axillary lymph nodes were also collected from some participants 
  • An enzyme linked immune absorbent spot assay was used to measure antibody-secreting plasmablasts (cells that differentiate into non-dividing plasma cells [aka antibody-secreting cells]) 

RESULTS

• 41 adults 
  • Evidence of previous SARS-CoV-2 infection: 8 participants 
  • Aspirates collected from lymph nodes: 14 participants 
• Circulating IgG- and IgA-secreting plasmablasts peaked one week after the second dose and then declined | Undetectable 3 weeks later 
  • Plasmablasts exhibited neutralizing activity against the early circulating SARS-CoV-2 strain and emerging variants 
  • Previously infected participants had the most robust serological response 
• Aspirates from the draining axillary lymph nodes identified germinal center B cells that bound the SARS-CoV-2 spike protein in all participants who had received first dose 
  • The draining lymph nodes sustained high levels of spike-binding germinal center B cells and plasmablasts for at least 12 weeks after the second dose 
• Spike-binding monoclonal antibodies derived from germinal center B cells mostly targeted the receptor-binding domain of the spike protein  
  • Fewer clones did cross-react and bind to the N-terminal domain or to epitopes shared with the spike proteins of human betacoronaviruses 
  • These cross-reactive clones had higher levels of somatic hypermutation vs those specific to SARS-CoV-2 spike protein, suggesting a memory B cell origin 

CONCLUSION

• mRNA-based COVID-19 vaccines induce a persistent germinal center B cell response, which leads to robust humoral immunity 
• The authors state 

To our knowledge, this is the first study to provide direct evidence for the induction of a persistent antigen-specific germinal centre B cell response after vaccination in humans 

Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination 

By inducing robust germinal centre reactions, SARS-CoV-2 mRNA-based vaccines are on track for achieving this outcome 

Learn More – Primary Sources: 

SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses 

mRNA COVID-19 Vaccine Safety in Pregnant Women

BACKGROUND AND PURPOSE:

• The clinical trials for mRNA-based COVID-19 vaccines did not include any pregnant women, so safety data in this group was initially limited
  • However, many pregnant women in the general population have since received these vaccines, providing a cohort in which to assess safety data
• Shimabukuro et al. (NEJM, 2021) reported preliminary findings regarding mRNA COVID-19 vaccine safety in pregnant persons from three U.S. vaccine safety monitoring systems

METHODS:

• Setting
  • United States
  • Data from December 14, 2020, to February 28, 2021
• Data sources
  • The “V-safe after vaccination health checker” surveillance system
  • The V-safe pregnancy registry | Telephone-based survey collects detailed information
  • The Vaccine Adverse Event Reporting System (VAERS)
• Primary outcomes
  • Non–pregnancy-specific adverse events
  • Pregnancy- and neonatal-specific adverse events

Note: Pregnancy and neonatal outcomes were derived from patients who enrolled in the registry

RESULTS:

• 35,691 v-safe participants self-identified as pregnant
  • Majority of the participants were
    • Between 25 to 34 years of age | Non-Hispanic White (approximately 75%)
• 3958 participants were enrolled in the registry

Vaccine-related side effects (V-safe)

• Injection-site pain was reported more frequently among pregnant women than among nonpregnant women
• The following were reported less frequently among pregnant women
  • Headache
  • Myalgia
  • Chills
  • Fever

Pregnancy Outcomes

• 827 participants completed pregnancy
  • Live birth: 86.1%
  • Spontaneous abortion: 12.6%
  • Stillbirth (0.1%)
  • Other outcomes (induced abortion and ectopic pregnancy): 1.2% 

Neonatal Outcomes

• Preterm birth: 9.4%
• Small for gestational age: 3.2%
• There were no neonatal deaths

Adverse Events (VAERS)

• 221 reports
  • Nonpregnant related: 70.1%
  • Pregnancy related: 29.9%
• Most frequently reported pregnancy-related adverse events
  • Spontaneous abortion (37 first trimester, 2 second trimester, 7 unknown or not reported)
  • No congenital anomalies (EUA reporting requirement)

CONCLUSION:

• While not directly comparable, the proportions of adverse outcomes in vaccinated women were similar to those reported in studies involving pregnant women before the pandemic
• Further longitudinal study is important, especially in women vaccinated in the first trimester
• The authors conclude that

Early data from the v-safe surveillance system, the v-safe pregnancy registry, and the VAERS do not indicate any obvious safety signals with respect to pregnancy or neonatal outcomes associated with Covid-19 vaccination in the third trimester of pregnancy

Learn More – Primary Sources:

Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons

Does COVID-19 Vaccination in Breastfeeding Women Produce Detectable Levels of Antibodies in Breast Milk?

BACKGROUND AND PURPOSE:

• Breastfeeding women were not included in COVID-19 vaccine trials, so there are limited data on vaccine-related safety in this group
• Perl et al. (JAMA, 2021) investigated whether maternal immunization led to detection of SARS-CoV-2 antibodies in breast milk

METHODS:

• Prospective cohort study
• Setting
  • Israel, between December 23, 2020, and January 15, 2021
• Participants
  • Breastfeeding women (exclusive or partial)
  • Elected to be vaccinated
• Exposure
  • All participants fully vaccinated with Pfizer-BioNTech vaccine
• Study design
  • Participants were recruited through advertisements and social media
  • Breast milk samples were collected
    • Before administration of the vaccine
    • Once weekly for 6 weeks starting at week 2 after the first dose
  • IgG and IgA antibody levels were assessed
  • Weekly questionnaires coupled to breast milk collection asked participants for information about interim well-being and vaccine-related adverse events
• Primary outcomes
  • Presence and levels of SARS-CoV-2 antibodies in breast milk

RESULTS:

• 84 women | 504 breast milk samples
  • Women: mean age 34 years
  • Infants: mean age 10.32 months
• Mean levels of SARS-CoV-2- IgA antibodies in breast milk increased rapidly and remained elevated throughout follow-up
  • 2 weeks after first dose: 61.8% of samples tested positive
  • 4 weeks after first dose: 86.1% of samples tested positive
  • 6 weeks after first dose: 65.7% of samples tested positive
• IgG antibodies remained low for the first 3 weeks, with an increase at week 4, which remained high throughout follow-up
  • 4 weeks after first dose: 91.7% of samples tested positive (P=0.004)
  • 5 and 6 weeks after first dose: 97% of samples tested positive
• Adverse events were experienced by a majority of women, but were generally mild, with local pain being the most common complaint
  • Reported events after the first dose: 55.9% of women
  • Reported events after the second dose: 61.9% of women
• No mother or infant experienced any serious vaccine-related adverse event
• Four infants developed a fever after maternal vaccination

CONCLUSION:

• Both IgA and IgG SARS-CoV-2 antibodies were detected in breast milk of vaccinated mothers
  • IgA presence was evident as early as 2 weeks after the first vaccine dose
  • IgG spiked 4 weeks after the first dose
  • IgA and IgG levels remained elevated throughout the follow-up period
• No major adverse events in mothers or infants were reported
• The authors conclude

Antibodies found in breast milk of these women showed strong neutralizing effects, suggesting a potential protective effect against infection in the infant 

Learn More – Primary Sources:

SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women

Potential Pathology Behind AstraZeneca COVID-19 Vaccination and Blood Clots

BACKGROUND AND PURPOSE:

• Schultz et al. (NEJM, 2021) describes 5 cases of severe thrombosis and thrombocytopenia following vaccination with the ChAdOx1 (AstraZeneca) COVID-19 vaccine

METHODS:

• Case reports
• Setting
  • Oslo University Hospital, Norway
• Cases included
  • 5 healthcare workers
  • 32 to 54 years old
• Study design
  • Serum antibodies tested (ELISA)
    • Platelet factor 4 (PF4)-polyanion complexes
    • SARS-CoV-2 spike and nucleocapsid proteins

RESULTS:

• 4 patients had severe cerebral venous thrombosis with intracranial hemorrhage | Fatal in 3 patients
• At time of admission
  • Levels of D-dimer were elevated in all patients
  • Screening for thrombophilia with proteins C and S and antithrombin was negative
• Platelet immunologic testing
  • All five patients had high levels of IgG antibodies to PF4–polyanion complexes
  • Platelets in serum from Patients 1, 3, 4, and 5 were clearly activated in the absence of added heparin
• All patients were negative for SARS-CoV-2 antibodies, suggesting previous infection was unlikely

CONCLUSION:

• 5 individuals developed severe venous thromboembolism in unusual sites and concomitant thrombocytopenia 7 to 10 days after vaccination (AstraZeneca)
• All 5 patients had a high level of antibodies to PF4–polyanion complexes
• The authors suggest

…that these cases represent a vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia (VITT)

Learn More – Primary Sources:

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination

COVID-19 mRNA Vaccine Effectiveness in the Real World Including in Those Partially Immunized

BACKGROUND AND PURPOSE:

• Both mRNA COVID-19 vaccines (Moderna and Pfizer/BioNTech) have been shown to be effective at preventing symptomatic COVID-19 in phase III trials
• Thompson et al. (CDC MMWR, 2021) quantified SARS-CoV-2 infections among vaccinated, partially-vaccinated, and non-vaccinated essential personnel every week for 12 weeks

METHODS:

• Prospective cohort study (December 14, 2020 to March 13, 2021)
• Setting
  • Eight locations in the US
• Participants
  • Health care personnel | First responders | Other essential and frontline workers
  • No previous laboratory documentation of SARS-CoV-2 infection
• Exposure
  • Vaccination status
    • Fully immunized (≥14 days after second dose)
    • Partially immunized (≥14 days after first dose and before second dose)
    • Unvaccinated
• Study design
  • The CDC tested for SARS-CoV-2 infections
    • Every week regardless of symptom status and
    • At the onset of symptoms consistent with COVID-19–associated illness
  • SARS-CoV-2 infections were confirmed by RT-PCR
• Statistical analysis
  • Authors accounted for time-varying vaccination status
  • Results adjusted for site

RESULTS:

• 3,950 participants with no previous SARS-CoV-2 infection
  • Fully immunized: 62.8%
  • Partially immunized: 12.1%
• SARS-CoV-2 infection
  • Unvaccinated: 1.38 infections per 1,000 person-days
  • Fully immunized: 0.04 infections per 1,000 person-days
  • Partially immunized: 0.19 infections per 1,000 person-days
• Estimated mRNA vaccine effectiveness for prevention of infection
  • Full immunization: 90%
  • Partial immunization: 80%

CONCLUSION:

• Both mRNA COVID-19 vaccines are effective at preventing infection, both symptomatic and asymptomatic, in essential personnel in real world conditions
• The authors conclude

These interim vaccine effectiveness findings for both Pfizer-BioNTech’s and Moderna’s mRNA vaccines in real-world conditions complement and expand upon the vaccine effectiveness estimates from other recent studies and demonstrate that current vaccination efforts are resulting in substantial preventive benefits among working-age adults

They reinforce CDC’s recommendation of full 2-dose immunization with mRNA vaccines

COVID-19 vaccination is recommended for all eligible persons 

Learn More – Primary Sources:

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021

An Update on COVID-19 Vaccine Related Anaphylaxis: Cases Remain Rare

BACKGROUND AND PURPOSE:

• Initial reporting rates of anaphylaxis in the US
  • Moderna: 2.5 cases per million doses (December 14 to 23, 2020)
  • Pfizer-BioNTech: 11.1 cases per million doses (December 21 to January 10, 2021)
• Shimabukuro et al. (JAMA, 2021) provide an update regarding anaphylaxis rates following vaccination

METHODS:

• Data sources
  • Vaccine Adverse Event Reporting System (VAERS)

RESULTS:

• Doses administered in US between December 14, 2020 and January 18, 2021
  • Moderna: 7,581,429 doses
  • Pfizer-BioNTech: 9,943,247 doses
• There were 66 total anaphylaxis cases after vaccine administration
  • Moderna: 19 total cases
    • Reporting rate 2.5 cases per million doses
  • Pfizer-BioNTech: 47 total cases
    • Reporting rate 4.7 cases per million doses
• Anaphylaxis case characteristics
  • Median (range) minutes to symptom onset
    • Moderna: 10 minutes (1 to 45 minutes)
    • Pfizer-BioNTech: 10 minutes (<1 minute to 19 hours)
  • Occurred in persons with a history of allergic reactions
    • Moderna: 84%
    • Pfizer-BioNTech: 77%
  • Occurred in persons with a history of anaphylaxis
    • Moderna: 26%
    • Pfizer-BioNTech: 34%
• No deaths have been reported due to vaccine-related anaphylaxis

CONCLUSION:

• Millions of doses of the Moderna and Pfizer-BioNTech COVID-19 vaccines have been administered in the US
  • Anaphylaxis is a rare event
  • The reporting rate is 2.5 (Moderna) and 4.7 (Pfizer-BioNTech) cases per million doses
• Immediate epinephrine administration is indicated for all cases of anaphylaxis
• The authors conclude

When considered in the context of morbidity and mortality from COVID-19, the benefits of vaccination far outweigh the risk of anaphylaxis, which is treatable 

Learn More – Primary Sources:

Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 2020-January 18, 2021

CDC Reports on Pregnancy and COVID-19 Outcomes

SUMMARY:

The CDC MMWR published a paper with the goal of analyzing and comparing the clinical outcomes of COVID-19 in pregnant and non-pregnant women aged 15 to 44 years. The study aimed to identify differences in symptoms, comorbidities, hospitalization rates, ICU admissions, mechanical ventilation needs, and maternal mortality between these two groups.

Summary of MMWR study

Methods

• CDC receives reports of COVID-19 cases through
  • Electronic standardized case report form or The National Notifiable Diseases Surveillance System
  • Data updated by health departments
  • Case reports for this study: January 22 to June 7 and updated as of June 17, 2020
• Participants
  • Women aged 15 to 44 years (reproductive age) from 50 states, the District of Columbia, and New York City
  • Lab confirmed SARS-CoV-2 infection
• Data collected included
  • Demographics | Pregnancy status | Underlying medical conditions | Clinical course | Outcomes (maternal)
• Missing data
  • To avoid overestimating the risk for adverse outcomes, “Outcomes with missing data were assumed not to have occurred (i.e., if data were missing on hospitalization, women were assumed to not have been hospitalized)”
• Statistical analysis
  • Outcomes: Logistic regression, using crude and adjusted risk ratios and 95% CIs
  • Risk ratios (RR) adjusted for
    • Age | Presence of underlying chronic conditions | Race/ethnicity

Results

• Women of reproductive age and positive for SARS-CoV-2: 326,335
• Pregnancy status
  • 28% (91,412) of all reproductive age women had pregnancy status available | Among those women with pregnancy information, 9% (8,207) were reported as pregnant
• Symptoms
  • Cough: Similar between pregnant and nonpregnant women (>50%)
  • Shortness of breath: Similar between pregnant and non-pregnant (30%)
  • Pregnant women less frequently reported
    • Headache | Muscle aches | Fever | Chills | Diarrhea
• Comorbidities
  • More frequently reported in pregnant women
    • Chronic lung disease | Diabetes mellitus | CVD
• Hospitalization
  • Significantly higher in pregnant women (adjusted)
  • Pregnant: 31.5% | Nonpregnant: 5.8%
  • aRR: 5.4 (95% CI, 5.1 to 5.6)
• ICU admission
  • Significantly higher in pregnant women (adjusted)
  • Pregnant: 1.5% | Nonpregnant: 0.9%
  • aRR: 1.5 (95% CI, 1.2 to 1.8)
• Mechanical ventilation
  • Significantly higher in pregnant women (adjusted)
  • Pregnant: 0.5% | Nonpregnant 0.3%
  • aRR: 1.7 (95% CI, 1.2 to 2.4)
• Maternal mortality
  • There was no difference between groups
  • Pregnant : 0.2% (16 patients) | Nonpregnant: 0.2% (208 patients)
  • aRR: 0.9 (95% CI, 0.5 to 1.5)

Conclusions

• Limitations include
  • Pregnancy status was missing for approximately 75% of women of reproductive age
  • Data on race/ethnicity, symptoms, underlying conditions, and outcomes were missing “for a large proportion of cases”
  • Data not available for the following
    • Trimester at time of infection was not available
    • Whether hospitalization was related to COVID-19
  • Current routine case surveillance does not capture pregnancy or birth outcomes
• CDC concludes that

These findings suggest that among women of reproductive age with COVID-19, pregnant women are more likely to be hospitalized and at increased risk for ICU admission and receipt of mechanical ventilation compared with nonpregnant women, but their risk for death is similar

Learn More – Primary Sources:

CDC (MMWR): Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020

ACOG: Novel Coronavirus 2019 (COVID-19)

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?

RECOVERY RCT ALERT: Dexamethasone Reduces COVID-19 Deaths

SUMMARY:

The ‘Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial’ is a national program in the UK to study multiple potential therapies for SARS-CoV-2 infection. The program involves thousands of doctors, nurses, pharmacists, and research personnel. The dexamethasone branch of the RECOVERY Trial program was halted on June 8th because the steering committee felt there was sufficient evidence to make a determination whether there was benefit to this therapy. The chief investigators, Professors Horby and Landray, reported the findings on June 16, 2020.

• The preliminary results found that

Overall dexamethasone reduced the 28-day mortality rate by 17% (0.83 [0.74 to 0.92]; P=0.0007) with a highly significant trend showing greatest benefit among those patients requiring ventilation (test for trend p<0.001)

Methods

Randomized controlled trial (RCT)

• Participants
  • Patients hospitalized with COVID-19
• Randomization
  • Dexamethasone 6 mg daily (oral or IV) vs usual care alone
• Primary Outcomes
  • Within 28 days after randomization: Death | Discharge | Need for ventilation | Need for renal replacement therapy
• Additional data collected
  • Age | Sex | Major co-morbidity | Pregnancy | COVID-19 onset date and severity

Results

• Dexamethasone group: 2104 patients | Usual care alone: 4321 patients
• Usual care group
  • 28-day mortality rates
    • Requiring ventilation: 41%
    • Oxygen only: 25%
    • No respiratory intervention: 13%
• Dexamethasone group: Reduction in deaths vs usual care alone
  • Requiring ventilation: Rate ratio (RR) 0.65 (95% CI, 0.48 to 0.88]; p=0.0003)
  • Oxygen only: RR 0.80 (95% CI, 0.67 to 0.96; p=0.0021)
  • No respiratory intervention: RR 1.22 (95% CI, 0.86 to 1.75; p=0.14)
• Need to treat
  • Ventilated patients: 1 death would be prevented by treatment of approximately 8 patients
  • Oxygen alone: 1 death prevented by treatment of approximately 25 patients

KEY POINTS:

• Reduction in deaths for hospitalized patients with COVID-19 with the use of low dose dexamethasone
  • Reduced deaths by one-third in ventilated patients
  • Reduced deaths by 20% for oxygen only patients   
  • No benefit for patients not requiring respiratory support
• Full report will be published
• Professor Hornsby, one of the chief investigators states that

…dexamethasone should now become standard of care in these patients. Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide

Learn More – Primary Sources:

RECOVERY TRIAL: Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report (NEJM)

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