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
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
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
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
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
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
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
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
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.
Respiratory Support of Pregnant Women with COVID-19 Including Fetal Assessment Recommendations
SUMMARY:
Although overall respiratory management is similar for pregnant women with COVID-19 compared to the general population, there are certain issues that are unique to this group. In addition, fetal wellbeing needs to be taken into consideration. This expert review by Pacheco et al. (Green Journal, 2020) provides key management points for treating patients with COVID-19 related respiratory compromise during pregnancy.
Management Algorithm
Pregnant Patient with Confirmed or Suspected COVID-19 and SpO2 <94%
Initial management
Conventional O2 therapy*: Target range 94% to 96%
Consider self-awake prone position
Limit fluids
Ensure airway expert is aware of patient
If patient not improving using conventional oxygen delivery methods
Reduce flow 5 to 10 L/min every 4 to 6 hours when an FiO2 of 0.4 to 0.5 is reached
Target SpO2 level >94%
If patient still does not improve
Consider intubation and invasive mechanical ventilation
*Conventional Oxygen Delivery Methods
Conventional Nasal Cannula
O2 flow: 1 to 6 L/min
O2 concentration: 24% to 40%
Conventional face mask
O2 flow: Set between 5 and 10 L/min
O2 concentration: Typically 40%
Venturi mask
Same as conventional face mask, but operator has more control over FiO2
Partial rebreather mask
Set O2 flow ≥10 L/min
O2 concentration: 60% to 70%
Nonrebreather mask
Set O2 flow ≥10 L/min
O2 concentration: 80%
**Requirements for high-flow nasal cannula
Ensure patient is
Hemodynamically stable with normal mental status
Can protect her own airway: Clear own secretions and good cough reflex
KEY POINTS:
Fetal Assessment for Patients with COVID-19 Respiratory Failure
<23 to 24 weeks
Fetal monitoring is not recommended
Stable and on conventional oxygen delivery system or high-flow nasal cannula
>24 weeks: Daily NST
Mechanical ventilatory support
24 to 28 weeks: Individualize based on multiple clinical factors including EFW, NICU support, maternal body habitus and availability of PPE
>28 weeks: Continuous monitoring
If patient’s respiratory status is deteriorating
Especially >28 weeks, the authors recommend:
…proceeding with a controlled delivery (likely cesarean) instead of awaiting fetal distress from refractory hypoxemia and needing an emergent delivery in the intensive care unit
Note: Authors caution that it is still important to weigh risks and benefits of fetal monitoring due to the significant risks associated with emergency cesarean delivery in patients with impaired respiratory function | Delivery “does not improve respiratory status of patients with acute respiratory failure” although authors acknowledge that this statement is based on limited evidence
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)
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
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
NOTE:Guidance has been updated to include the latest ACOG statement regarding gyn patient prioritization. Information and guidelines may change rapidly. Check in with listed references in ‘Learn More – Primary Sources’ to best keep up to date.
SUMMARY:
ACOG has released FAQs that address common questions faced by those healthcare professionals providing gynecologic care. The recommendations in this document reinforce CDC guidance and clarify some issues specific to gynecology. Below are highlighted FAQs from the document (please see ‘Learn More – Primary Sources’ below for link to complete document). ACOG states that
Determining how best to care for patients given the COVID-19 pandemic depends on the patient’s signs and symptoms, the patient’s comorbidities and underlying medical condition, the acuity of the presentation (eg, acute versus chronic condition), available health resources, and other factors
Change in practice prioritization is based on resource reduction resulting from the current COVID-19 pandemic
ACOG provides examples (“list is not meant to be exhaustive”)
In-person appointment
Fever risk for gyn infection
Ectopic
Post-op complications not suitable for phone
Heavy vaginal bleeding with signs/symptoms suggestive of anemia
By telehealth (includes virtual visit or phone)
Contraceptive management
Asymptomatic ovarian cyst
Menopause management
Routine gyn or post-op care
Routine medication abortion care
Mental or behavioral health screening
“May potentially” defer till after COVID-19
Preventive visits
Routine screenings for average-risk patients
Patient Prioritization: GYN Surgeries
ACOG emphasizes that decisions related to surgical triage should be based on disease severity, not necessarily a particular surgical procedure
ACOG along with multiple other gynecology societies, released a joint statement on the suspension of elective surgeries during the COVID-19 pandemic
The joint statement supports the Surgeon General’s statement to modify surgical scheduling if the patient will not be harmed by delay
If a delay will impact patient health and cause harm, the surgery should be performed as scheduled
SGO recommendations
Examples of surgeries that could be potentially delayed include
Benign-appearing ovarian cysts | Hysterectomy for menorrhagia without evidence of anemia
Surgeries for precancerous lesions or low risk for endometrial cancer (especially in healthy patients)
Examples of surgeries that should not be delayed
Most cancer surgeries
Resections of masses that will cause end-organ damage or impair quality of life
KEY POINTS:
Abortion Services
Due to its time-sensitive nature, ACOG states that “Abortion is an essential component of comprehensive health care”
Furthermore, ACOG and other gynecology societies released a joint statement supporting access to abortion services during the COVID-19 pandemic
To decrease risk of exposure and transmission, strategies include
Counsel remotely (video or phone)
Offer timely referral if practice does not provide service
If no risk factors for ectopic pregnancy and patient has regular menses with a known LMP
Assess gestational age remotely | Ultrasound not required
If uncomplicated, pre-op visit and consent can be done remotely (video or phone)
“Routine in-person or video or telephone visits are not necessary after an uncomplicated abortion procedure”
Medical abortion
Assessment, counseling, and consent can be done remotely (by video or telephone)
Mifepristone and misoprostol can be self-administered at home
Follow-up after an uncomplicated medication abortion can be done remotely (video or telephone) | In-person visit not required
Note: ACOG states “The FDA has lifted additional burdens on patients seeking access to and clinicians prescribing mifepristone for pregnancy termination and miscarriage during the COVID-19 public health emergency. As you consider changes to your clinical practice, however, please take several important factors into account. Whether you now have authority to mail mifepristone is a fact-specific, state-specific legal question. We strongly encourage any clinician seeking this relief to consult with a lawyer before making any changes to your clinical practice.”
Rh testing and RhD immunoglobulin administration
Should not be a barrier to the provision of medication abortion
Low risk of sensitization
NSAIDS
No evidence of association between NSAIDs, such as ibuprofen, and COVID-19 exacerbation | Situation may change in the future with further information
Continue to offer low-dose aspirin and other NSAIDs as medically indicated
Antibody Testing
Some institutions are testing all patients prior to procedures
Antigen testing
Remains the test of choice for diagnosis
Antibody (serologic) testing
Not diagnostic
Can be used to obtain information that may indicate prior exposure
At present, it is unclear if antibodies confer immunity
The document states that antibody testing
…should not be used as the sole basis to diagnose COVID-19, to determine staffing decisions or decisions regarding the need for personal protective equipment (PPE), or to determine if a person has immunity to COVID-19
Breast Imaging and Post-Vaccine Lymphadenopathy
COVID-19 vaccination may be associated with temporary contralateral or ipsilateral lymphadenopathy
A Radiology Scientific Expert Panel has addressed this issue, as the nodal enlargement identified on breast imaging may be difficult to distinguish from lymph node enlargement seen with malignancy
Vaccination should not be delayed due to imaging needs, including indications related to cancer or screening
“The estimated infection fatality risk of COVID-19 is orders of magnitude higher than the estimated mortality reduction achieved through effective cancer screening programs in the general population”
If possible, mammograms should be conducted prior to COVID-19 vaccination
Following vaccination and to avoid complicating interpretation of imaging results
Urgent cancer-related clinical indications (e.g., acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications): Do not delay breast imaging
All other indications (routine surveillance, screening, staging): Consider postponing imaging for ≥6 weeks after completion of recommended vaccinations
Note: The Society of Breast Imaging recommends delay of 4 to 6 weeks
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