Updates to the Living Treatment Guideline
Seven new treatment recommendations for pregnant and breastfeeding women
Sotrovimab for pregnant women
Following recent recommendations for the use of sotrivamab in adults, the Taskforce has reviewed the evidence in the context of pregnant and breastfeeding women. Three new recommendations have been developed for the use of sotrovimab in pregnant women, reflecting the adult recommendations.
The recommendations also include additional information in the remark recognising that pregnant and breastfeeding women were not included in the COMET-ICE Trial, and there are currently no data on the effects of sotrovimab on a pregnant woman or baby.
The Taskforce also notes that sotrovimab is a human immunoglobulin G (IgG) and may cross the placenta from mother to baby. The potential impact of this is not known. However, it is known that pregnant women with COVID-19 are at increased risk of developing severe disease, which can be detrimental to the health of the woman and her baby. Sotrovimab can therefore be considered if the benefit justifies the potential risk.
Casirivimab plus imdevimab (REGEN-COV) for pregnant and breastfeeding women
The Pregnancy and Perinatal Care Panel has also reviewed the casirivimab plus imdevimab for adults recommendation and have developed three new recommendations for pregnant and breastfeeding women that reflect the guidance for adult patients.
In patients hospitalised with moderate to critical COVID-19 who are seronegative for SARS-CoV-2 antibodies, casirivimab plus imdevimab probably reduces the risk of death.
The Taskforce notes that while pregnant and breastfeeding women were eligible for the RECOVERY Trial, there is currently insufficient evidence to evaluate maternal and fetal safety. Hence, it should only be used in pregnant and breastfeeding women if the potential benefit outweighs the potential risk for the mother and fetus.
In response to questions from frontline clinicians, the Pregnancy and Perinatal Care Panel have developed a consensus recommendation to support the use of magnesium sulphate as per usual care. The Panel determined that there are substantial benefits for using magnesium sulfate for fetal neuroprotection in preterm birth, and for management of pre-eclampsia and eclampsia. There is currently no direct evidence to suggest additional harms of using magnesium sulfate for fetal neuroprotection in the setting of COVID-19.
New conditional recommendation for casirivimab plus imdevimab (REGEN-COV) for post-exposure prophylaxis
The Disease-Modifying Treatment and Chemoprophylaxis Panel has reviewed the results from the COVID-19 Phase 3 Prevention Trial Team, a large randomised study including over 1500 patients.
The Panel concluded that the use of prophylactic casirivimab plus imdevimab probably reduces the risk of symptomatic and asymptomatic COVID-19 infection in seronegative household contacts of individuals with confirmed COVID-19 when used within 4 days of exposure. In settings for which serology testing is not readily available, consider using in unvaccinated household contacts who return a negative PCR result and who are considered unlikely to have had previous SARS-CoV-2 infection.
As a result the Taskforce recommends:
Consider using subcutaneous casirivimab plus imdevimab as prophylaxis in seronegative or PCR-negative close household contacts of individuals with confirmed COVID-19.
Currently casirivimab plus imdevimab is not available for use within Australia.
The Taskforce is currently developing specific recommendations on the use of casirivimab plus imdevimab as prophylaxis for pregnant women, children and adolescents. These will be published in a future version of the guidelines.
Further details about these recommendations and additional updates are below.
Taskforce and member organisations highlight ivermectin recommendation
In response to ongoing media coverage surrounding the use of ivermectin, the Taskforce together with our 32 member organisations highlights our recommendation that ivermectin should only be used for the treatment of COVID-19 in the context of randomised trials with appropriate ethical approval.
All Taskforce recommendations are based on the best available global evidence and developed by more than 250 of Australia’s leading clinical experts. Recommendations are then approved with 100% consensus by the 32 Taskforce members—Australia’s peak medical colleges and health bodies.
To support clinicians in providing evidence-based advice regarding the use of ivermectin as a treatment for COVID-19, the Taskforce has also created a one-page pdf that covers our most frequently asked questions. This is available for download from the website and will be updated as new and reliable evidence emerges.
COVID-19 research pipeline
Consider using sotrovimab for the treatment of COVID-19 within five days of symptom onset in pregnant women in the second or third trimester who do not require oxygen and who have one or more additional risk factors for disease progression..
Within the population of pregnant women for which sotrovimab is conditionally recommended for use (as listed above), decisions about the appropriateness of treatment with sotrovimab should be based on the patient’s individual risk of severe disease, on the basis of multiple risk factors, and COVID-19 vaccination status.
Consider using sotrovimab in unvaccinated or partially vaccinated patients and patients who are immunosuppressed regardless of vaccination status
Do not routinely use sotrovimab in fully vaccinated patients unless immunosuppressed.
Given the absence of evidence evaluating the effectiveness of sotrovimab for pregnant and breastfeeding women and SARS-CoV-2 variants of concern, rigorous data collection should be undertaken on indications and key outcomes for patients who receive treatment with sotrovimab.
The use of magnesium sulfate in pregnancy for fetal neuroprotection for women at risk of preterm brith is supported as part of standard care, independent of the presence of COVID-19.
The use of magnesium sulfate in pregnancy for the management of severe pre-eclampsia or eclampsia is supported as part of standard care, independent of the presence of COVID-19.
Consider using casirivimab plus imdevimab in pregnant or breastfeeding women who are seronegative patients hospitalised with moderate to critical COVID-19.
Do not use casirivimab plus imdevimab in pregnant or breastfeeding women who are seropositive patients hospitalised with moderate to critical COVID-19.
Only in research
Do not use casirivimab plus imdevimab in pregnant or breastfeeding women who are mild or asymptomatic outpatients with COVID-19 outside of randomised trials with appropriate ethical approval.
Consider using subcutaneous casirivimab plus imdevimab as prophylaxis in seronegative and PCR-negative household contacts of individuals with confirmed COVID-19.
One new trial has been added to the evidence base for prone positioning for adults. The ‘consensus recommendation’ promoting the consideration of prone positioning for at least 3 hours per day as tolerated has been upgraded to a ‘conditional recommendation’.
The Taskforce is continually monitoring research to update recommendations as new evidence emerges.
11 clinical flowcharts have been developed by the Taskforce to cover:
Changes to the flowcharts this week reflect:
We are currently reviewing evidence to develop recommendations and flowcharts to guide practice in areas including:
The full list of Cochrane Reviews and related COVID-19 content from the Cochrane Library can be found here.
It is a core mission of the Taskforce to engage with frontline clinicians to rapidly identify and address priority clinical questions.
Each week we collect suggestions for new clinical questions or topics for consideration by the Taskforce. A document that lists all of the suggested questions, topics and new patient groups that we have received to date is available here.
Please encourage your clinical colleagues to provide their insights via the website.