Journal club papers
- This paper presents the general management recommendations for pregnant patients with COVID-19 infection, based on the experiences of clinicians in Hubei province, China.
- Timing of birth – COVID-19 infection is not an absolute indication for delivery; expedited delivery should be decided on a case-by-case basis depending on maternal disease progression, gestational age and fetal intrauterine condition
- Early delivery should be considered if COVID-19 infection is not improved by supportive treatment or if the maternal condition is considered severe/critical and delivery is indicated for maternal safety (to improve oxygenation)
- Mode of birth – mode of birth should be based on obstetric indications, acknowledging that the safety of vaginal delivery vs caesarean section in COVID-19 patients has not yet been established.
- Consider lowering the threshold for caesarean section in the first stage of labour in order to reduce the duration of labour/inpatient stay and minimise the exposure of other women and healthcare workers to an infected patient.
- Biospecimens of vaginal secretions, umbilical cord, amniotic fluid, placenta and neonatal throat swab should be taken to determine potential intrauterine vertical transmission
- All delivery instruments should be labelled COVID-19 and sterilised separately
- All staff in attendance should be monitored for signs of infection
- Delivery room and infection precaution – delivery should take place in a negative pressure isolation room (or infection isolation room), remove all unnecessary items from the room, minimise attending staff, full PPE should be worn by staff in attendance with strict handwashing precautions to be observed and patients should wear a surgical mask during delivery (unless under general anaesthetic)
- Anaesthesia – epidural anaesthesia is generally recommended for COVID-19 infected patients to reduce the exacerbation of infection during intubation/extubation and minimise the impact of GA on the newborn
- Neonatal management – A paediatrician/neonatologist should be present at delivery
- Newborns of a confirmed or suspected COVID-19-infected mother should be transferred to the neonatal isolation ward immediately – if the mother is confirmed COVID-negative, the newborn should be returned to the mother, if the mother tests positive for COVID-19, the newborn should remain in quarantine for 14 days.
- This paper reported the findings of a small cohort study of 33 COVID-19 infected pregnant patients and their newborns (N=3 infected neonates) in Wuhan, China
- The most common symptoms amongst the neonates was shortness of breath (4/33), with chest XR findings shown to be non-specific and no deaths reported
- Of the three COVID-19 infected neonates, all were diagnosed with COVID-19 on day 2 of life and all had negative swabs by day 7
- The most seriously ill COVID-19 affected neonate was delivered prematurely (31+2/40) due to fetal distress in the setting of maternal pneumonia, and had confirmed bacterial sepsis (Enterobacter positive blood cultures) – the authors report that these factors are more likely to have caused respiratory distress than SARS-CoV2 infection
- The authors propose that the source of neonatal infection for the affected neonates is likely to be maternal, however they also report that all samples including amniotic fluid, cord blood and breastmilk were negative for SARS-CoV-2
- The details of the ‘strict infection control procedures’ followed at the time of delivery are not reported
- The paper emphasises the importance of screening pregnant women, implementing strict infection control measures, quarantining infected mothers and close monitoring of neonates at risk of COVID-19
Including the papers reviewed last week, there are now over 75 reported cases of pregnant women infected with COVID-19. Reassuringly, all have done well and there is no strong evidence of vertical transmission – we will continue to keep you updated as new findings are reported.
Hydroxychloroquine, typically used to treat autoimmune disease, has been touted as a potential treatment for COVID-19. However, its true effectiveness remains unclear, with human trials providing conflicting results. In short, more well designed RCTs are required. Given the ongoing media and political coverage of hydroxychloroquine we have included 3 of the most recent human trials investigating this as a COVID-19 treatment.
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Gautret et al, International Journal of Antimicrobial Agents. 20/03/20
(Link provides full-text article)
- This open-label, non-randomized, single arm trial treated 26 cases of confirmed COVID-19 infection with 600 mg hydroxychloroquine daily for 10 days, 6 patients also received daily azithromycin. Results were compared against 16 untreated patients (those who declined treatment, had an exclusion criterion or were treated at another centre).
- 6 days after inclusion SARS-CoV-2 clearance was assessed (primary outcome) and clinical characteristics evaluated throughout.
- 6 HCQ treated patients were lost to follow up and not included in the analysis; 3 were transferred to ICU, 1 died, 1 left the hospital and 1 stopped treatment due nausea.
- By day 6, 14/20 (70%) of the HCQ treated patients, including 6/6 HQC + azithromycin treated, were negative for SARS-CoV-2. Whilst, among the untreated patients only 2/16 (12.5%) were negative for SARS-CoV-2.
Although these results appear promising there are some important limitations:
- Non-randomized - meaning the groups may not be comparable.
- Small number of participants.
- Untreated participants included those who were ineligible for HCQ and cases from other centres, which may result in selection bias.
- Exclusion of patients lost to follow-up, 5 of whom had severe outcomes including 1 death, which may skew the results.
These findings provide conflicting results to the previous study (20% vs 100% clearance). However, due to the small study size and lack of comparison arm it is again difficult to draw meaningful conclusions from these results.
Correspondence: No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Molina et al, M´edecine et Maladies Infectieuses. 30/03/20
- Following the rapid viral clearance found in the first study, the same dosing regimen of HCQ + azithromycin was followed in a separate single-arm study which treated 11 patients for 10 days.
- 5 days after commencing treatment 1 patient died and 2 were transferred to ICU.
- By day 6, 10/11 patients were retested for SARS-CoV-2 (the patient who died was not tested), of which only 2/10 were negative.
- 62 patients with confirmed COVID-19 infection were enrolled in a blinded, randomized, control trial and received either standard treatment or standard treatment + hydroxychloroquine at 400 mg/day.
- 5 days after inclusion, time to clinical recovery and clinical characteristics were evaluated.
- Compared to the control group, the HCQ group experienced a shorter body temperature recovery time (2.2 days vs 3.2 days) and cough remission time.
- Progression to severe disease occurred in 0/31 in the HCQ group and 4/31 in the control group.
- Pneumonia was assessed via chest CT and improved by day 6 in 25/31 in the HCQ group and 17/31 in the control group.
- In the HCQ group, two patients experienced adverse reactions; 1 with body rash and 1 with headache.
Thus far, this is the largest and most well-designed study investigating HCQ to treat COVID-19. However, it is still small, did not investigate viral clearance and most importantly, has not yet undergone peer-review. More studies are needed before HCQ should be used clinically to treat COVID-19. Fortunately, these are underway and include the WHO SOLIDARITY trial which will recruit thousands of patients across 70 countries and investigate four potential treatments including hydroxychloroquine – watch this space.