Discussion
Main findings
We retrospectively analysed prospectively collected data of pregnant women infected with 2019-nCoV in their second and third trimester. Of all patients presenting in the 2nd or 3rd trimester, 15/23(65%) cases had mild manifestation; and 7/23(30%) cases were severe presenting with pyrexia and showing evidence of pneumonia on chest x ray examination, only one case had no symptoms related to 2019-nCoV infection before birth, and fever occurred after delivery. Two of the severe cases 2/23(8.7%) progressed to critical illness, both cases were in the 3rd trimester, and one of them had a known diabetes.
Four neonates with suspected infection due to raised inflammatory markers, white cell count or pyrexia had pharyngeal swabs taken. SARS-CoV-19 was not detected in the throat swab by RT-PCR in any of their neonates, suggesting that there is no direct evidence of maternal-fetal vertical transmission in COVID-19 infection in late pregnancy.
Interpretation
It is well known that IgG is passively transferred across the placenta from mother to fetus beginning at the end of the second trimester and reaches high levels at the time of birth11Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia.JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4861.. However, IgM is not usually transferred from mother to fetus because of its larger macromolecular structure. Alternatively, IgM could have been produced by the infant if the virus crossed the placenta 11.
On the contrary, regardless of the report by Chen et al,5 all maternal lung Chest x rays showed typical changes of viral pneumonia, suggesting that the lung CT did not have a more important clinical diagnostic value in terms of diagnosis.
The immune function of pregnant women is relatively suppressed during pregnancy. At the same time, physiological changes during pregnancy will also expose pregnant women to a higher risk, which will lead to adverse outcomes 22Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G. Viral infection during pregnancy. Am J Reprod Immunol. 2015 Mar; 73(3):199-213. Epub 2015 Jan 13.,33Gil M, Ingrid C. Immune System in Pregnancy: A Unique Complexity. Am J Reprod Immunol. 2010 Jun; 63(6): 425–433.. It is reported in the literature that pregnant women infected with SARS-CoV may have more adverse pregnancy outcomes (spontaneous abortion, intrauterine growth retardation and premature delivery, etc.); the mortality rate of pregnant women is as high as 25% 44AJOG-MFM. Outcome of Coronavirus Spectrum Infections (SARS, MERS, COVID-19) during Pregnancy: A Systematic Review and Meta-Analysis. Available from: Https://Www.Ajog.Org/Coronavirus_guidance_ajog_mfm.; 2020., which is higher than that of ordinary infected people (case fatality rate is about 10%). In a review of 11-pregnant women infected with MERS-CoV, 90% had adverse outcomes and 3 died 55Schwartz DA, Graham AL. Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and other human coronavirus infections [J]. Viruses, 2020,12 (2). pii: e194. DOI: 10.3390 / v12020194.. Recently, Chen et al.5, and Zhu et al.66Zhu HP, Wang L, Fang CZ, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoVpneumonia [J / OL]. Transl Pediatr. (2020-02-10) [2020-02-11]. Https: //dx.doi.org/10.21037/tp.2020.02.06. reported that the perinatal infection 2019-nCoV may have adverse effects on newborns, but compared with SARS-CoV, the adverse mother-to-child outcomes are fewer. However, the pathological changes of the placenta after 2019-nCoV infection are not yet clear 77Ng WF, Wong SF, Lam A, et al. The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation [J]. Pathology, 2006,38 (3): 210-218. DOI: 10.1080 / 00313020600696280..
Also, there was a relatively higher rate of preterm birth, preeclampsia, and caesarean in hospitalised mothers infected with COVID-19 in this study. 7/19 (37%) of the patients who acquired the infection in the 3rd trimester had preterm delivery, which remains higher compared to the national rate of preterm delivery (7.3%) 88National Institute for Health and Care Excellence [NICE], Preterm labour and birth (NG25) available on the NICE website:https://www.nice.org.uk/guidance/ng25..Furthermore, the rate of C-section in our study was 16/19 (84%) which is significantly higher than the national C-section rate in the UK (26.2%) 99NHS Maternity statistics, England 2018-19. Available:https://digital.nhs.uk/data-and-information/publications/statistical/nhs-maternity-statistics/2018-19..Out of all patients 2/19 (10.5%) had severe pre-eclampsia compared to (1-2%) risk in general population 19, out of which one patient developed HELLP, and disseminated intravascular coagulation (DIC).
Only one pregnancy with confirmed COVID-19 infection was complicated by SGA.
The only placental histological study on SARS 1010English FA, Kenny LC, McCarthy FP. Risk factors and effective management of preeclampsia. Integr Blood Press Control. 2015; 8:7‐12. Published 2015 Mar 3. doi:10.2147/IBPC.S50641.,retrospectively analysed the placental tissue of 7-pregnant women infected with SARS-CoV. The authors found that the placental tissues of pregnant women who were infected with SARS-CoV in early pregnancy were normal; the placental tissues of pregnant women in the acute stage of SARS had large amount of fibrin deposition between the chorionic and chorionic villi with abnormal blood flow in the placenta suggesting fetal thrombosis, vascular disease or disseminated intravascular coagulation.
The current national guideline for PPE advises clinician working within two metres of a confirmed or suspected COVID-19 patient to wear an apron, gloves, a surgical mask and eye protection. Clinicians carrying out tasks that could generate airborne droplets are required to use an even higher standard of protection, including disposable gowns, filtering respirators and face shielding visors 1111Department of health and social care. Covid-19: Personal Protective Equipment (PPE) Plan. April 2020.https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/879221/Coronavirus__COVID-19-personal_protective_equipment__PPE__plan.pdf. .
In our study, all hospitalised women with confirmed COVID-19 had surgical masks on. The full PPE protection including FFP3 masks were only used for aerosol-generating procedures to minimise the need for PPE which remains compliant with WHO recommendations, however, 28.8% of patients with suspected infection were reviewed by clinicians without FFP3 masks, and had confirmed COVID-19 infection on nasopharyngeal swabs taken during the review. Furthermore, this was compliant with local institutional protocol which was based on WHO recommendations22.
In view of the global shortage in PPE supply, WHO also recommends considering the reuse of PPE until confirmation of adequate re-supply is in place 1212Organization W.H. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. Updated March 2020.https://apps.who.int/iris/bitstream/handle/10665/331498/WHO-2019-nCoV-IPCPPE_use-2020.2-eng.pdf..
NHS England and Public Health England (PHE) have agreed that NHS Supply Chain for PPE needs to continue to meet the demand for health care workers especially in view of lack of effective viral-specific treatments and the high case–fatality rate 1313Considerations for acute personal protective equipment (PPE) shortages Updated 3 May 2020. https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/managing-shortages-in-personal-protective-equipment-ppe..
Strengths and limitations
This study is limited by the small sample size, lack of amniotic fluid analysis to confirm vertical transmission of infection, and by incomplete information on the outcome of the infants beyond the end date of data collection. We are acknowledging the limited number of cases reported to date, however, our findings are important for understanding the characteristics of the disease in pregnant women, and the outcome in infants whose mothers are infected with SARS-CoV-2. In our study, we reviewed the compliance in the use of (PPE) in view of the huge challenge in supply to NHS workers, especially in view of global demand, and shortage.