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)

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

Neonatal Infection: COVID-19 and Risk for Vertical Transmission

PURPOSE:

• Walker et al. (BJOG, 2020) sought to investigate the risk for vertical transmission in women with COVID-19 around the time of delivery
• A systematic analysis was performed, including an effort to address duplicate reporting in previous studies

METHODS:

• Systematic review and critical analysis (Search from April through May, 2020)
  • Authors sought out full text copies of any studies that may be eligible for inclusion
• Eligibility criteria for studies
  • Pregnant women with confirmed (positive test or high clinical suspicion) COVID-19
  • Case reports or case series | No language restriction
• Rates of infection were determined for the following
  • Mode of birth (cesarean or vaginal)
  • Breast or formula feeding
  • Rooming in or isolation
• Studies underwent disambiguation to avoid duplication of patients among different reports

RESULTS:

• 49 studies included
  • 666 neonates | 655 pregnant women
  • 11 twins
• Infected neonates: 4%
• Duplicate pregnancies (in Chinese data) were identified and were properly accounted for in subsequent analyses

Mode of Delivery

• Neonatal infection rates based on mode of delivery
  • Vaginal delivery: 2.7%
  • Cesarean: 5.3%

Breast vs Formula Feeding

• Among neonates with confirmed COVID-19
  • Breast fed: 7
  • Formula: 3
  • Expressed breast milk: 1
  • Unreported: 17

Rooming In vs Isolation

• Among neonates with confirmed COVID-19
  • Isolated: 7
  • Rooming in: 5
  • Not reported: 16

CONCLUSION:

• Overall, there was a low rate of neonatal infection following maternal COVID-19 infection
• There does not appear to be a greater risk for vertical SARS-CoV-2 transmission based on mode of delivery, breast feeding or rooming in
• The authors acknowledge limitations including
  • Not all newborns tested for SARS-CoV-2
  • Case series have possibility of bias | More severe cases are more likely to be reported
  • “…disappointing that details of outcome and care” were not available and should be considered a “missed opportunity”
  • Due to low newborn infection rate, ‘n’ of infected neonates is still relatively small and appropriate caution should be used in interpreting the data
• The authors conclude that

There is no evidence that isolating the baby away from the mother is beneficial if such precautions are taken, and encouraging the baby to spend time with its mother is likely to help with breastfeeding and bonding

We recommend that separation only occurs where this is necessary for clinical indications

Learn More – Primary Sources:

Maternal transmission of SARS‐COV‐2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis

Do Warmer Temperatures Decrease the Incidence of COVID-19?

BACKGROUND AND PURPOSE:

• Sehra et al. (Clinical Infectious Diseases, 2020) investigated the effects of temperature, precipitation, and UV Light on community transmission of SARS-CoV-2

METHODS:

• Observational analysis of case data
• Data analyzed (January 22 to April 3, 2020)
  • Daily reported cases of SARS-CoV-2 and daily weather patterns across the US
• Analysis
  • Null hypothesis: There is no association between daily temperatures and COVID-19 spread
  • Modeling techniques were used to investigate whether daily maximum temperature, precipitation, UV Index and the SARS-CoV-2 incidence 5 days later were related
  • Sensitivity analyses to assess transmission lags were performed at 3 days, 7 days and 9 days

RESULTS:

• 974 daily observations
• Max temperature of >52°F associated with a lower rate of new cases at 5 days
  • Incidence rate ratio (IRR) 0.85 (95% CI 0.76 to 0.96; p = 0.009)

Temperature

• Temperature <52°F was inversely associated with case rate at 5 days
  • IRR 0.98 (95% CI 0.97 to 0.99; p = 0.001)
• Modeling results: Rate of new cases was lower for theoretical states where daily temperature remained >52°F
  • At this temperature threshold, modeling predicted that there would be 23-fewer cases per-million per-day by 25 days of the epidemic

UV Index

• A 1-unit higher UV index associated with a lower rate at 5 days
  • IRR 0.97(95% CI 0.95 to 0.99; p = 0.004)

Precipitation

• Precipitation was not associated with a greater rate of cases at 5 days
  • IRR 0.98 (95% CI 0.89 to 1.08; p = 0.65)

CONCLUSION:

• COVID-19 incidence was lower at warmer vs cooler temperatures
  • Incidence declined with increasing temperature until 52°F
• The authors state that while statistically significant, the actual association is small and therefore

…unlikely to provide significant effect beyond current strategies for mitigation

…although there is an association between daily temperature and subsequent case volume the disease may continue to spread in the United States even in periods of warmer weather

Learn More – Primary Sources:

Maximum Daily Temperature, Precipitation, Ultra-Violet Light and Rates of Transmission of SARS-Cov-2 in the United States

Remdesivir RCT Results: 5 or 10 Day Treatment for Severe COVID-19?

BACKGROUND AND PURPOSE:

• Remdesivir is an RNA polymerase inhibitor that has antiviral activity against RNA viruses, possibly including SARS-CoV-2
• Goldman et al. (NEJM, 2020) sought to evaluate the efficacy and safety of a 5-day vs 10-day course of remdesivir for the treatment of severe COVID-19

METHODS:

• Randomized, open-label, phase III clinical trial (RCT)
• Participants
  • Hospitalized COVID-19 (confirmed) patients
  • Oxygen saturation <94% on room air
  • Radiologic evidence of pneumonia
• Intervention
  • 5 days IV remdesivir
  • 10 days IV remdesivir
• Study design
  • Patients were randomly assigned 1:1
  • All patients received
    • 200 mg of remdesivir on day 1
    • 100 mg of remdesivir on all subsequent days
• Primary outcome
  • Clinical status on day 1 using a 7-point ordinal scale from days 1 to 14 or until discharge | Worst score (lowest) recorded each day
• Statistical analysis
  • 400 patients (200 in each group)
  • >85% power to detect an odds ratio (OR) for improvement of 1.75
  • Two-sided significance level of 0.05

RESULTS:

• 397 patients began treatment
  • 5-day group: 200 patients
    • Median duration of treatment: 5 days
  • 10-day group: 197 patients
    • Median duration of treatment: 9 days
• 10-day group had significantly worse clinical status at baseline but otherwise 2 groups were demographically balanced
• Primary outcome
  • There was no statistical difference in clinical improvement between groups at 14 days once adjusting for baseline clinical status (P=0.14)
• Nor were there any differences in secondary outcomes including
  • Time to recovery
  • Proportion of patients who recovered by days 5, 7, 11 and 14
  • Death from any cause
• The most common adverse effects (5-day vs 10-day)
  • Nausea: 10% vs 9%
  • Acute respiratory failure: 6% vs. 11%
  • Increased ALT: 6% vs 8%
  • Constipation: 7% in both groups
• Discontinuation of treatment due to adverse events
  • 4% in the 5-day group vs 10% in the 10-day group
• Post hoc analysis was performed to determine if there was benefit for any subgroups
  • Patients who progressed to mechanical ventilation: Death by day 14
    • 5-day group: 40%
    • 10-day group: 17%

CONCLUSION:

• There was no significant difference in patient outcomes with a 5- or 10-day course of remdesivir in patients with severe COVID-19
• These results can not be extended to patients who are ventilated as most patients were not receiving respiratory support prior to receiving remdesivir
• The authors note that there was no placebo arm and therefore this study could not determine the efficacy of remdesivir
• The authors state

Our trial suggests that if remdesivir truly is an active agent, supplies that are likely to be limited can be conserved with shorter durations of therapy

Learn More – Primary Sources:

Remdesivir for 5 or 10 Days in Patients With Severe Covid-19

RCT Results: Does Hydroxychloroquine Work for COVID-19 Postexposure Prophylaxis?

PURPOSE:

• Boulware et al. (NEJM, 2020) sought to determine if hydroxychloroquine can be used to prevent COVID-19 in individuals who have been exposed to SARS-CoV-2

METHODS:

• Randomized, double-blind, placebo-controlled trial (RCT)
• Participants:
  • Asymptomatic
  • Household or occupational exposure to individual with confirmed COVID-19 | <6 feet distance for >10 minutes
    • High-risk exposure: No face mask or eye shield
    • Moderate-risk exposure: Face mask but no eye shield
• Randomization within 4 days post-exposure
  • Hydroxychloroquine: 800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days
  • Placebo
• Primary outcome
  • New COVID-19 (lab confirmed or compatible symptoms if testing unavailable) within 14 days
• Secondary outcomes included
  • Hospitalization | Death | PCR-confirmed SARS-CoV-2 infection | Symptoms (severity)
• Statistical analysis
  • Two-sided alpha of 0.05 | 90% power | 50% relative effect size
  • Require 750 participants in each group

RESULTS:

• 821 participants
  • Hydroxychloroquine: 414
  • Placebo: 407
• High-risk exposure: 87.6%
• New illness compatible with COVID-19
  • No difference was detected between groups
    • Hydroxychloroquine: 11.8%
    • Placebo: 14.3%
  • Absolute difference: −2.4 percentage points (95% CI, −7.0 to 2.2; P=0.35)
• Side effects where higher in the hydroxychloroquine group, although no severe side effects were reported
  • Hydroxychloroquine: 40.1%
  • Placebo: 16.8%

CONCLUSION:

• The trial was stopped during interim analysis due to futility, with no significant difference between groups
• The authors concluded

High doses of hydroxychloroquine did not prevent illness compatible with Covid-19 when initiated within 4 days after a high-risk or moderate-risk exposure

Learn More – Primary Sources:

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

Is Blood Viscosity Greater in Patients with Severe COVID-19?

PURPOSE:

• Coagulation disorders and thrombosis are recognized COVID-19 complications, particularly for patients with severe disease
• Maier et al. (Lancet, 2020) found evidence for multiple anticoagulation failures at their institution among patients with severe COVID-19
• Therefore, the authors sought to identify other mechanisms to explain ‘refractory hypercoagulability’ (i.e. when prophylactic/ therapeutic dosing of medications such as heparin do not prevent significant VTE)

METHODS:

• Case series
• Participants
  • COVID-19 pneumonia, critically ill and admitted to the ICU
• Testing
  • Capillary viscometry which tests for plasma viscosity

RESULTS:

• 15 patients included
  • Intubation for ARDS: 14 patients
  • Shock requiring vasopressors: 12 patients
  • Renal failure (on renal replacement therapy): 11 patients

Anticoagulation

• D-dimer ≥3 μg/mL
  • Clinical concern for thrombotic event: 5 patients received therapeutic anticoagulation | 2 patients received IV heparin and 3 patients received direct thrombin inhibitor (argatroban or bivalirudin)
  • No clinical concern for thrombotic event: 6 patients received intermediate dosing (subtherapeutic) of LMWH or IV heparin
• D-dimer <3 μg/mL: 4 patients received low dose thromboprophylaxis with LMWH or subcutaneous heparin

Viscosity Testing Results

• All patients had plasma viscosity measurements >95% normal
  • 1.9 to 4.2 centipoise | Normal range 1.4 to 1.8
• 4 patients >3.5 centipoise had thrombotic events
  • PE | limb ischemia and PE | Renal treatment related clotting (2 patients)
• Centipoise levels were highly correlated with disease severity (p<0.001)

Fibrinogen Levels

• Fibrinogen results significantly elevated
  • Median fibrinogen: 708 mg/dL (range 459 to 1188) | Normal reference range 200 to 393

CONCLUSION:

• Hyperviscous plasma can damage endothelium and lead to thrombosis
• Patients with severe COVID-19 had significantly increased plasma viscosity compared to normal range
  • Plasma viscosity was highly correlated with disease severity
• Cellular components associated with inflammation (e.g. fibrinogen or immunoglobulin) can lead to increased viscosity
• The authors conclude that

Our novel observation might provide an important link between inflammation and coagulopathy in critically ill patients with COVID-19

We are actively exploring any beneficial role of therapeutic plasma exchange, a highly effective treatment for symptomatic hyperviscosity in other conditions such as hypergammaglobulinaemia, in the clinical management of these patients

Learn More – Primary Sources:

COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?

Placental Findings Associated with COVID-19

PURPOSE:

• Shanes et al. (American Journal of Clinical Pathology) sought to identify placental pathology associated with COVID-19 infection

METHODS:

• Case control study
• Histologic evaluation of the placenta was performed
  • Cases: Placentas from pregnant women with confirmed SARS-CoV-2 infection who delivered between March 18, 2020 and May 5, 2020
  • Historical controls
    • Placental samples derived from women who had placental evaluation for maternal/fetal indications (e.g, FGR, chorioamnionitis)
    • History of melanoma | Considered a superior control because evaluation would be performed for potential metastases rather than possible confounding indication (e.g. SGA)
• Prior to April 7, only patients with moderate to severe disease were tested | Following this date, all women admitted to labor and delivery underwent testing

RESULTS:

• 16 placentas from women with COVID-19 were evaluated
• Gestational Age at delivery
  • Term deliveries (37 to 40 weeks): 14
  • 34 week delivery: 1
  • 16 week IUFD: 1
• Placental size
  • SGA: 5
  • LGA: 1
• Indication for placental exam
  • SARS-CoV-2: 13
  • Cholestasis in pregnancy and GDM: 1
  • Pregnancy-induced hypertension: 1
  • IUFD (above): 1
• Timing of COVID-19 diagnosis
  • Remote from delivery (25 to 34 weeks): 4
  • 6 to 7 days prior to delivery: 2
  • At time of admission for delivery: 10
• Clinical COVID-19 course
  • Symptomatic: 10 patients
  • Oxygen requirement: 2
  • Maternal deaths or requiring intubation: 0
  • All infants had normal Apgar scores and discharged home except for 34 week delivery who was still in NICU
• 16 week IUFD: Retroplacental hematoma | Removed from analysis of placental findings because controls were all from 3rd trimester deliveries

Placental Findings

• Placentas from COVID-19 pregnancies were more likely to have ≥1 feature of maternal vascular malperfusion (MVM) compared to
  • Melanoma controls: Odds ratio (OR) 7.3 (P = .001)
  • Other historical controls: OR 3.4 ( P = .046)
• Individual MVM features were more likely be found in COVID-19 pregnancies
  • Decidual arteriopathy vs both control groups
  • Atherosis and fibrinoid necrosis vs both groups
  • Peripheral villous infarction vs melanoma group
• Features of fetal malperfusion (FVM) were also more common in the COVID-19 placentas vs both control groups such as delayed villous maturation
• Findings associated with acute and chronic inflammation were not increased

CONCLUSION:

• MVM reflects abnormalities in oxygenation within the intervillous space and is associated with adverse perinatal outcomes, including hypertensive disorders and preeclampsia
• Despite MVM findings, only 1 patient with COVID-19 had hypertension
• The authors conclude that the changes found in the placentas from pregnant women with COVID-19

…may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology

…these findings suggest that increased antenatal surveillance for women diagnosed with SARS-CoV-2 may be warranted

Learn More – Primary Sources:

Placental Pathology in COVID-19

Low Prevalence of COVID-19 Positive Test Results on Labor Floor Outside NYC Region

PURPOSE:

• Campbell et al. (JAMA, 2020) sought to determine the prevalence of positive SARS-CoV-2 test results in pregnant population admitted for delivery in Southern Connecticut

METHODS:

• Quality improvement project (April 2 to 29, 2020)
• Patients admitted for delivery underwent screening and testing
  • 3 Yale New Haven Health hospitals
• Screening Questions
  • Travel | Contacts | COVID-19 symptoms
• Testing for SARS-CoV-2
  • Patients without a prior diagnosis of COVID-19
  • Nasopharyngeal swabs: Rapid testing available
  • Scheduled cesarean: Tested preoperatively
• Healthcare personnel prevention protocol
  • Universal mask use (patients, clinicians, and support persons) | 1 support person visitor per patient
  • Symptomatic patients: Clinicians wear N95 respirators and PPE until results available | Continued if test positive
  • Asymptomatic patients: Usual precautions including masks
  • Second stage and delivery: Full PPE and N95 respirators for positive or no test result

RESULTS:

• 782 patients screening | 1.5% (n=12) previously diagnosed with COVID-19
• 770 patients tested
  • SARS-CoV-2 positive: 3.9% (n=30)
  • 73.3% of positive cohort were asymptomatic
• Overall prevalence of SARS-CoV-2 among asymptomatic women admitted for delivery
  • 2.9% (22/756)
  • No patients developed symptoms
• Symptomatic patients with a positive test: 57% (8/14)
• SARS-CoV-2 prevalence over time increased in asymptomatic women and decreased in symptomatic women
  • First 2 weeks
    • Asymptomatic: 0.6%
    • Symptomatic: 1.4%
  • Second 2 weeks
    • Asymptomatic: 5%
    • Symptomatic: 0.7%
• Healthcare personnel
  • No healthcare workers were exposed or developed COVID-19 due to known or possible patient exposure

CONCLUSION:

• Low prevalence of positive SARS-CoV-2 testing among asymptomatic pregnant patients admitted for delivery outside endemic NYC region
  • Prevalence of 2.9% in current study vs 13.5% in previous NYC study (see ‘Related ObG Topics’ below)
• Connecticut is considered an affected region with the 3rd highest COVID-19 death rate per capita
• The authors suggest that

Approaches to care that balance screening and testing of patients combined with a rationalized approach to use of PPE should be considered for obstetric units.

Learn More – Primary Sources:

Prevalence of SARS-CoV-2 Among Patients Admitted for Childbirth in Southern Connecticut

ACOG COVID-19 FAQs for Obstetrical Care

NOTE: Information and guidelines may change rapidly. Check in with listed references in ‘Learn More – Primary Sources’ to best keep up to date. This entry has been updated with additional information on counseling patients working in a non-healthcare setting.

SUMMARY:

ACOG has released FAQs that address common questions faced by obstetrical care professionals. The recommendations in this document reinforce CDC guidance and clarify some issues specific to obstetrics. Below are highlighted FAQs from the document (please see ‘Learn More – Primary Sources’ below for link to complete document)

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• Masks
• Clinical Guidelines that Remain Unchanged
• Monoclonal Antibodies
• SARS-CoV-2 Protease Inhibitors in Pregnancy
• PPH: Use of TXA and Hemabate 
• Visitation Policies During COVID-19

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Masks

For Pregnant Women

• Not fully vaccinated
  • Wear a mask or cloth face covering in public and when around people outside of the household
  • ACOG recommends the above particularly when social distancing may not be doable
• Fully vaccinated
  • Follow CDC guidance | However, some pregnant women may wish to continue using masks and should be supported
• Healthcare settings, schools, public transport
  • Regardless of vaccine status, precautions including mask or cloth face covering should be used
  • CDC specifies cloth vs surgical masks or respirators, which should be reserved for healthcare personnel

Health Care Professionals (CDC Guidance)

• Source control options (prevent spread of respiratory secretions when breathing, talking, sneezing or coughing) for HCP include
  • NIOSH-approved N95 or equivalent or higher-level respirator or
  • A respirator approved under standards used in other countries that are similar to NIOSH-approved N95 filtering facepiece respirators (note: these should not be used instead of a NIOSH-approved respirator when respiratory protection is indicated) or
  • A well-fitting facemask
• When used solely for source control, any of the options listed above could be used for an entire shift unless they become soiled, damaged, or hard to breathe through
• If masks used for protective equipment (PPE) (e.g., NIOSH-approved N95 or equivalent or higher-level respirator during the care of a patient with SARS-CoV-2 infection, facemask during a surgical procedure or during care of a patient on Droplet Precautions) then discard after the patient care encounter
  • Healthcare providers should use PPE, including respirators or face masks, goggles, gowns and gloves | N95 respirators should be used for aerosol-generating procedures
  • ACOG states that “COVID-19 infection is highly contagious, and this must be taken into consideration when planning intrapartum care”

KEY POINTS:

Clinical Guidelines that Remain Unchanged

Continue to Manage According to Current Clinical Guidance

• Timing of delivery
  • COVID-19 should generally not impact timing of delivery
  • Exception: If a woman is infected in the third trimester and there are no medical indications to the contrary, “it is reasonable” to try and postpone delivery until there is a negative test result or quarantine lifted
• Induction of labor
• Operative delivery
• Mode of delivery
• Delayed cord clamping
• Antenatal fetal testing
• Antenatal fetal surveillance
  • Detailed mid-trimester anatomy scan “may be considered” after pre-pregnancy or first-trimester maternal infection
  • Interval growth assessments “could be considered depending on the timing and severity of infection”
  • Timing and frequency of ultrasound should take in to account clinical setting and additional maternal risk factors

Antenatal Fetal Surveillance: Additional Considerations

• Antenatal fetal surveillance
  • Detailed mid-trimester anatomy scan “may be considered” after pre-pregnancy or first-trimester maternal infection
  • Interval growth assessments “could be considered depending on the timing and severity of infection”
  • Timing and frequency of ultrasound should take in to account clinical setting and additional maternal risk factors

Anti-SARS-CoV-2 Monoclonal Antibodies

Monoclonal antibodies are recommended by the NIH for use in the following clinical scenarios (see ‘Related ObG Topics’ below for NIH COVID Treatment Guidelines)

• For patients with mild to moderate COVID-19 who are at high risk of clinical progression
  • Start treatment as soon as possible after positive SARS-CoV-2 antigen or NAAT report becomes available and within 10 days of symptom onset
• Post-exposure prophylaxis (PEP) should be considered for inadequately vaccinated individuals who have been exposed to SARS-CoV-2
  • These individuals include those who have had a recent exposure to an individual with SARS-CoV-2 for a cumulative total of ≥15 minutes over a 24-hour period or
  • There is a recent occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting AND are 1) not fully vaccinated or 2) fully vaccinated but may not mount an adequate immune response
• The NIH specifically addresses use of PEP in pregnancy and states

PEP should not be withheld from pregnant or lactating individuals who have been exposed to SARS-CoV-2, especially those with additional conditions that increase their risk of progressing to severe disease

Pregnant or lactating patients and their providers should determine whether the potential benefits of the drugs outweigh the potential risks

• ACOG supports the use of monoclonal antibodies in both clinical scenarios (risk for progression or PEP) and states the following

Pregnancy is included among the conditions that put individuals at high risk for clinical progression

This makes patients with pregnancy as their only risk factor eligible to receive outpatient monoclonal antibodies, according to the EUA (NIH)

Obstetric care clinicians may consider the use of monoclonal antibodies for the treatment of non-hospitalized COVID-19 positive pregnant individuals with mild to moderate symptoms, particularly if one or more additional risk factors are present (eg BMI >25, chronic kidney disease, diabetes mellitus, cardiovascular disease)

Lactation is not a contraindication for the use of monoclonal antibodies

Note: Some monoclonal antibodies that were effective against previous variants have limited effectiveness against Omicron variant and therefore ACOG recommends “physicians should consult their facilities as to which monoclonal antibody therapies against SARS-CoV-2 infection are available for treatment options”

SARS-CoV-2 Protease Inhibitors in Pregnancy

PAXLOVID          

• Oral medication
• Includes nirmatrelvir (SARS-CoV-2 main protease inhibitor) and ritonavir (HIV-1 protease inhibitor and CYP3A inhibitor)
• Available only under emergency use authorization (EUA)
• Recommended for the treatment of outpatients with mild to moderate COVID-19 infection who
  • Have a positive SARS-CoV-2 viral test
  • Are at higher risk of clinical progression
• Pregnancy
  • Pregnancy is a risk factor for clinical progression and therefore meets criteria for use of medication use, particularly if other high risk factors are pregnant (e.g., diabetes)
• Lactation
  • Breastfeeding is not a contraindication to use and can be used as indicated in this population
• Dosage
  • Start as soon as possible following diagnosis and within 5 days of symptoms
  • The dose for patients with normal renal function is nirmatrelvir 300 mg (two 150 mg tablets) plus ritonavir 100 mg (one 100 mg tablet) orally twice daily for 5 days

Note: There is risk for drug interactions including mediations used in pregnancy (e.g., nifedipine) | ACOG recommends that “Prescribing clinicians should consult the full prescribing information prior to and during treatment for potential drug interactions”

Fetal Risks

• Nirmatrelvir
  • Human study data
    • None available but observational data has not demonstrated increased risk for birth defects
  • Animal studies
    • Reduced fetal body weights noted among pregnant rabbits at doses 10 times higher than comparable typical human exposure
• Ritonavir
  • Used commonly for management of HIV during pregnancy, suggesting acceptable safety profile

Note: ACOG states that “short-term exposure to these medications must be balanced against the maternal and fetal risks associated with untreated COVID-19 in pregnancy”

PPH: Use of TXA and Hemabate

TXA

• COVID-19 appears to be a hypercoagulable state
• TXA can be considered for the treatment of PPH in keeping with guidance for non-COVID-19 patients
• However, the document states

Because of the possible additive effect of the increased risk of thrombosis from COVID-19 infection and the hypercoagulative state of pregnancy, it may be prudent to consider this increased likelihood of clotting before adminisitering TXA for postpartum hemorrhage

Hemabate

• While Hemabate is not used in asthma due to risk for bronchospasm, patients with COVID-19 have respiratory symptoms consistent with viral pneumonia
• While there is no data specific to COVID-19 and this medication, “Hemabate is not generally withheld” in patients with viral pneumonia

Visitation Policies During COVID-19

• Visitation policy decisions are ultimately guided by
  • Local facilities and capabilities (e.g., physical space, equipment)
  • Community spread and prevalence
  • Governmental regulations and recommendations at multiple levels
• ACOG recommends that for both inpatient and outpatient
  • Reduce number of visitors to minimum necessary
  • Limit to those individuals “essential for the pregnant individual’s well-being (emotional support persons)”
  • Screen all visitors for symptoms of respiratory illness
    • Patient should be attended to by an asymptomatic visitor
    • A visitor with fever or respiratory symptoms should not accompany the patient
• Additional support persons
  • Encourage the use of alternative forms of interaction (e.g., video-call apps)
• Counseling patients and families regarding restrictive visitation policies
  • Acknowledge value of support persons
  • Explain the temporary nature of the policies and that they are in place to protect everyone’s safety, including the patient, baby and community at large
• Special considerations for underserved communities
  • Support systems including support persons are especially important throughout the delivery journey, including postpartum care
  • ACOG states that

…institutions should be mindful of how restrictions might differentially and negatively affect these communities, which in many areas are also disproportionately affected by COVID-19

Learn More – Primary Sources:

COVID-19 FAQs for Obstetrician-Gynecologists, Obstetrics

Infection Control: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) | CDC