key: cord-0801849-rtilfnzi authors: Lambelet, Valentine; Vouga, Manon; Pomar, Léo; Favre, Guillaume; Gerbier, Eva; Panchaud, Alice; Baud, David title: Sars‐CoV‐2 in the context of past coronaviruses epidemics: Consideration for prenatal care date: 2020-05-26 journal: Prenat Diagn DOI: 10.1002/pd.5759 sha: 9129e4fb43a274037212b2ac835d2034d4c4fbdf doc_id: 801849 cord_uid: rtilfnzi Since December 2019, the novel SARS‐CoV‐2 outbreak has resulted in millions of cases and more than 200,000 deaths worldwide. The clinical course among non‐pregnant women has been described but data about potential risks for women and their fetus remain scarce. The SARS and MERS epidemics were responsible for miscarriages, adverse fetal and neonatal outcomes and maternal deaths. For COVID‐19 infection, only 9 cases of maternal death have been reported as of April 22, 2020 and pregnant women seem to develop the same clinical presentation as the general population. However, severe maternal cases, as well as prematurity, fetal distress and stillbirth among newborns have been reported. The SARS‐CoV‐2 pandemic greatly impacts prenatal management and surveillance and raise the need for clear unanimous guidelines. In this narrative review, we describe the current knowledge about coronaviruses (SARS, MERS and SARS‐CoV‐2) risks and consequences on pregnancies and we summarize available current candidate therapeutic options for pregnant women. Finally, we compare current guidance proposed by RCOG, ACOG and the WHO to give an overview of prenatal management which should be utilized until future data appear. This article is protected by copyright. All rights reserved. Severe cases of COVID-19 infection in pregnant women are not frequent as with the previous coronavirus infections described above. Nevertheless, nine (2.7%) maternal deaths have been reported among eleven Iranian patients with 3 rd trimester infections (44-46). All women presented with typical symptoms, including dyspnea. They were previously healthy except two patients known for hypothyroidism and one patient with suspected gestational diabetes. Maternal age was between 22 and 49 y.o. and two women had dichorionic/diamniotic twin gestations. All women were admitted to the ICU, intubated and ventilated and died from cardiopulmonary collapse or multiple organ failure (MOF). One had septic shock and disseminated intravascular coagulation (DIC) before progressing to heart failure. Intrauter ine fetal death (IUFD) were described among four patients (4/9) with gestational ages between 24 and 30 WG. CS were performed in other cases (5/9) with gestational age between 30 and 38 WG. Cohort studies have reported a rate of severe disease requiring ICU admission of 6.9-8% (n=9/118; n=8/116), including 3 requiring mechanical ventilation among Chinese patients. In the Italian cohort, a total of 17% of pregnant women (n=7/42) required either oxygen supplementation through continuous positive airway pressure (CPAP) or ICU admission, while in the American cohort, 4 (9.3%) presented with severe disease and 2 (4.7%) required ICU admission without mechanical ventilation. Severe complications in pregnant women are similar to what has been described in the general population and include multiple organ failure, respiratory failure requiring mechanica l ventilation, and even Extracorporeal Membrane Oxygenation, as described in a patient at 35 WG (47). In the latter, the patient required an emergency cesarean section for maternal resuscitation and the newborn unfortunately died due to an intrauterine asphyxia. The mother had multiple organ failure, needed mechanical ventilation before Extracorporeal Membrane Oxygenation for a total of 7 days. She was discharged from hospital 6 weeks later. Two cases of cardiomyopathy related to COVID19 were reported by Juusela and al. (48) . The first pregnant woman was 45 y.o., had a BMI of 44.6 m 2 /kg and was diagnosed with dietcontrolled gestational diabetes. She delivered via cesarean at 39 WG for severe preeclamps ia and tested positive to SARS-CoV-2 on postpartum day 1 with evidence of fever, tachypnea and suspicious chest imaging. She was then diagnosed with acute heart failure after an echocardiogram was performed, showing a moderately reduced left ventricular ejection fraction (LVEF) of 40% with global hypokinesis. On day 5 postpartum, the mother required This article is protected by copyright. All rights reserved. mechanical ventilation and was still intubated at the time of publication. The second patient was a 26 y.o. women with no relevant medical history. She was admitted for respiratory symptoms necessitating nasal oxygen support. Due to the previous experience, an echocardiogram was completed and showed a moderately reduced LVEF of 40-45% with global hypokinesis. She rapidly developed severe features leading to a cesarean section at 34 WG. At the time of publication, she was postpartum day 1 and did not require oxygen support. Though current data suggest that most pregnant women with COVID-19 will have an uncomplicated clinical course, severe complications must be anticipated. Nevertheless, the observed rates appear similar to those for non-pregnant patients between 20-40 years old. In a recent analysis based on a Chinese cohort, the actual rate of severe disease was 173/1170 (9.8%) among 20-39 y.o. patients; after adjusting for demographic factors, the expected rate of severe disease was 0.6-8.6% (21) . Breslin et al. also reported a similar rate of complications in pregnant women compared to nonpregnant adults (11) : 86 vs 80 % with mild clinical symptoms, 9.3 vs 15 % with severe symptoms and 4.7 vs 5% requiring ICU admission respectively. We should point out, however, that complications in the general population mainly impacted the elderly and patients with comorbidities. When comparing pregnant woman to their typical age group, they qualify as a high-risk group for adverse maternal outcomes (49). Therefore, although the majority of infected pregnant women seems to demonstrate a mild clinical course, pregnancies should be approached with caution considering the potential critica l complications reported in several cases published so far report. More exhaustive data, however, This article is protected by copyright. All rights reserved. are needed to understand the additional risk pregnancy may pose to women with a COVID-19 infection. SARS-CoV-1 and MERS-CoV infections during pregnancy were associated with adverse fetal and neonatal outcomes. A report on twelve pregnant women suffering from SARS-CoV-1 (2002-03 pandemic) was published (50) and the rate of adverse fetal / neonatal outcomes was 66% (8/12) in this series. Four of the seven patients (57%) infected during the first trimester experienced miscarriages. Two others decided to terminate their pregnancy after recovering from SARS, and the last had an uncomplicated pregnancy. Among the five patients infected during the second or third trimester, four (4/5, 80%) had a preterm delivery, including one for fetal distress (1/5, 20%) . Two neonates exhibited respiratory distress syndrome and other complicatio ns related to prematurity (necrotizing enterocolitis). All placentas of these patients (5/5, 100%) weighed below the 5 th percentile, of which 2 had abnormal anatomo-pathology results (thrombotic vasculopathy with avascular fibrotic villi and / or placental infarct) (51). When the infection occurred during the week before birth, no fetal growth restriction was noted (0/2). When the infection occurred one month or more before birth, two fetuses (2/3, 33%) had fetal growth restriction (FGR) with oligohydramnios, related to the abnormal placentas presented above. Another Chinese series (52) reported fetal demise in one of five (20%) fetuses exposed to SARS-COV-1 during the second or third trimester of pregnancy. This article is protected by copyright. All rights reserved. Eleven fetuses / neonates from mothers infected with MERS-CoV have been described (53)(54)(55). Among them, 3 (3/11, 27%) had fetal or neonatal demise: two intrauterine fetal deaths at 20 and 34 weeks, and one neonatal demise at 24 weeks due to extreme prematurity (55)(56). Abruption was identified on placental examination from these fetuses, and from another liveborn neonate who presented with fetal distress at 37 weeks (57). With regards to SARS-CoV-2 infection during pregnancy, several case-series and case reports show that similar adverse fetal and neonatal outcomes could occur. Overall, we included 142 cases with fetal and/or neonatal outcomes available at the time of this review. Among them, 40 (28%) were born prematurely (<37w) and 20 (14%) had adverse outcomes (FGR, fetal or neonatal demise, severe symptoms at birth). Congenital or perinatal transmiss io n was suspected in 6 of 115 (5%) newborns tested. Details of all cases available are presented in Table 1 . In a case-control study (58), among 17 fetuses from SARS-CoV-2 infected mothers, 3 exhibited FGR (3/17, 18%), 2 had fetal distress (2/17, 12%), and four were born prematurely (4/17, 24%) due to PROM or placental bleeding. The rates of low birth weight and premature birth were significantly higher when compared to the control groups. One of these fetuses also exhibited sinus tachycardia that persisted after birth. Zhu and colleagues (59) described the outcomes of 10 neonates from SARS-CoV-2 infected mothers. Two of them were small for gestational age (2/10, 20%), and 6 had a Pediatric Critical Illness Score (PCIS) below 90 with shortness of breath (6/10, 60%), fever (2/10, 20%), thrombocytopenia accompanied by abnormal liver This article is protected by copyright. All rights reserved. function (2/10, 20%), tachycardia (1/10, 10%), vomiting (1/10, 10%), and pneumothorax (1/10, 10%). Neonatal radiography showed abnormalities in 7 of them (7/10, 70%): 4 had signs of infection, 2 respiratory distress syndrome and 1 pneumothorax. Among these neonates, two (2/10, 20%) had disseminated intravascular coagulation and one (1/10, 10%) refractory shock with multiple organ failure leading to death at day 8 of life. Liu Y. (60) presented the outcomes of 10 other newborns exposed during pregnancy: none which were positive for SARS-CoV-2 at birth, 6 (6/10, 60%) were premature (for fetal distress in 3 cases, 3/10, 30%), and one was stillborn (1/10, 10%). Chen and colleagues (61) described a series of 9 newborns from infected mothers during the third trimester. Two (2/9, 22%) had a low birthweight and four (4/9, 44%) were premature (for fetal distress in 2 cases), none experienced a severe adverse outcome. Yu and colleagues also reported a series of 7 newborns from infected mothers during the third trimester, without adverse outcomes. One of these neonates had a positive SARS-CoV-2 PCR 36 hours after birth, leading to the suspicion of a perinatal transmission. Liu D. and colleague s (62) described briefly the outcomes of 13 newborns from infected mothers. Induced prematurity was noted in 54% (7/13), but none had neonatal complications. In the New-York series (42), which presented the outcomes of 18 infants from infected mothers, all but one had negative neonatal testing for SARS-CoV-2. One infant had an 'indeterminate' test result, which was clinically managed as a 'presumptive negative' diagnosis, as this result may reflect low level detection. In this series, 3 (3/18, 17%) instances of fetal distresses were noticed, one infant (1/18, 6%) was premature and one (1/18, 6%) presented with RDS with a concern for sepsis. Zeng and colleagues (63) reported the largest series to date, with 33 newborns included. A perinatal infection was suspected in three of them (3/33, 9%), with a positive PCR at day 2 and 4 of life. Infected newborns presented with higher rates of FGR, prematurity and complicatio ns at birth (fever, pneumonia, RDS, shortness of breath) than non-infected newborns: 33% vs 7%, 33% vs 10 %, 100% vs 10%, respectively. Wang (64) reported one case with a positive PCR in both the mother and her newborn (whereas placental and umbilical blood samples were negative). This newborn had lymphocytopenia, abnormal liver function and elevated creatine kinase, although was clinically stable. Congenital or perinatal transmission was also suspected in three other cases (65) (66) . SARS-CoV-2 IgM antibodies were elevated in these three newborns, although their nasopharyngeal PCRs were negative. In an editorial related to these cases, Kimberlin (67) pointed out that false-positive results due to cross-reactivity of IgM could occur and perinatal testing remains a challenge. Interestingly, Zamaniyan and al.(68) , described a case of positive SARS-CoV-2 amniot ic sample from a newborn, raising concern about potential vertical transmission in mothers with serious illness. Indeed, possible vertical transmission has been questioned by other authors (65, 66) and remain unclear. A case of second trimester miscarriage was reported by Baud and al.(69) in a patient at 19 WG positive for SARS-CoV-2. Virological findings confirmed the presence of the virus in the placenta, but not in fetal tissue or maternal samples, suggesting a potential impact of SARS-CoV-2 early in the pregnancy. In other CoV infections during the second or third trimester of pregnancy, it is interesting to note that placental changes seem to precede FGR. Severe maternal respiratory illness related to CoV infection may lead to a circulatory insufficiency in both the placenta and the fetus. Thus, This article is protected by copyright. All rights reserved. a maternal COVID infection could affect the oxygen supply, leading to placental insufficienc y, IUGR, fetal distress and / or fetal demise. A direct impact of the virus itself, by increasing fibrin deposits or thrombo-embolic events in the placenta, cannot be excluded and warrants further investigation. Similarly, maternal SARS related to CoV-2 infection during the first trimester of pregnancy could disrupt the uterine placental flow, leading to miscarriage. Although the risk of miscarria ge has been described with SARS-CoV-1 infection, no cases have yet been reported with SARS-CoV-2 infection. Currently, no curative agent has been found for COVID-19. Studies conducted so far (includ ing randomized controlled trials = RCTs) have been plagued by poor methods and reporting, such as exclusion of patients with worse outcome from the treated group, different endpoints between protocols and published reports, premature stopping of RCT (leading to lack of statistical power), use of endpoints of no clinical value (such as viral load), degrees of severity of enrolled patients (so that the benefit of a treatment or lack thereof in a cohort of patients may not generalizable to patients with different degrees of severity, lack of optimization of treatment dose or duration of treatment, to name but a few). This article is protected by copyright. All rights reserved. Several drugs are currently being evaluated as potential treatment for SARS-CoV-2 includ i ng hydroxychloroquine, lopinavir-ritonavir combination, remdesivir, oseltamivir, Interferon alpha, darunavir, baricitinib, tocilizumab and immunoglobulin therapy. Hydroxychloroquine use in pregnant women has raised concerns in the past especially for an increased risk of cardiac malformation (70) and its retinal and ototoxicity (71)(72), related to the use of chloroquine and not hydroxychloroquine, findings which were not confirmed in more recent case series (73)(74)(75) (76) . In the most recent systematic review and meta-analys is conducted in 2016, Kaplan YC et al (77) , found no increase "in the rates of major congenita l craniofacial and cardiovascular, nervous system and genitourinary malformations in the infants." However, there was a significant increase in the spontaneous abortion rate, which could be associated with the underlying disease activity rather than the treatment. That being said, (hydroxy)chloroquine is one of the antimalarial drugs considered compatible with pregnancy in all trimesters for prophylaxis and treatment of malaria (78, 79) . A recent article gathered evidence on its use during lactation and found that it was compatible with breastfeeding (80), concluding that hydroxychloroquine could be used for the treatment of COVID-19 infection, in usual rheumatological doses (200-400 mg/day) if proven to be effective. The lopinavir ritonavir combination is used as part of the HAART regimen to treat HIV infected women during pregnancy (81) . In a systematic review that included 4,864 LPV/r-exposed pregnancies, the authors reported the rate of congenital abnormalities to be similar to that of the general population. However, the stillbirth rate was higher than in the general population in the UK (9.2 per 1000 infants against 4.7 per 1000 infants in 2013) (82). There has been general concern regarding protease inhibitor exposure in utero and its association with an increased risk of preterm birth (83), however, to our knowledge this risk has not been evaluated specifica lly for lopinavir and ritonavir alone, and could be associated with the underlying disease activity rather than the treatment. Finally, moderate adverse events such as gastro-intestinal symptoms (84) and an increased risk for alteration in fasting glycemia (85) were reported. Lopinavir and ritonavir are drugs considered compatible with pregnancy in all trimesters for HIV treatment and has been associated with very low excretion into breastmilk (78, 79) . Regarding remdesivir, no adverse effect was reported in pregnant participants in a randomized controlled trial on Ebola virus (86). Safety data on remdesivir in pregnancy are still scarce. Oseltamivir was used during the 2009 influenza A/H1N1 pandemic and notably in pregnant mothers. In the most recent population-based study (87) conducted on 946,176 pregnancies in Denmark from 2002 to 2013 of which 1898 were exposed to oseltamivir during pregnancy, Ehrenstein.V and colleagues found no increased risk of any major congenital malformatio n, fetal death, preterm birth, SGA or low 5-min APGAR score. This confirmed previous observations from the European registry study (88) and the Roche Global Safety Database (89). Oseltamivir could be considered compatible with pregnancy in all trimesters if proven effective in COVID-19 treatment and has been associated with very low excretion into breastmilk (78, 79) . The Interferon alpha drug (INFα) is used to treat essential thrombocythemia, chronic myelocytic leukemia or hepatitis B and C in pregnant women. In a recent review including 43 exposed women, Sakai K et al. found that no adverse event had required discontinuation of the This article is protected by copyright. All rights reserved. treatment but alerted physicians to "pay attention to (…) rare adverse events, such as impaired liver function, interstitial pneumonia, and attempts at suicide" (90). Safety data on INFα in pregnancy are scarce but its similarity to beta interferon, of which safety data during pregnancy are substantial and reassuring, makes it compatible in pregnancy if proven effective for COVID-19 infection. Regarding darunavir, no embryotoxicity or teratogenicity of this molecule was found in anima l studies (91). In a brief review of darunavir use in pregnant women, the authors concluded that it is a well-tolerated molecule which has few minor adverse effects (92). Darunavir is considered compatible with pregnancy in all trimesters for HIV treatment despite its lack of safety data in pregnancy as its maternal benefit outweighs the potential unknown risks (78, 79) . Animal studies have demonstrated embryotoxicity of baricitinib (93) and no safety data are available in human. Analysis of the Roche Global Safety Database does not suggest a substantially increased risk of malformations with the use of Tocilizumab. However, an increased rate of preterm birth and low birth weight children was possibly associated with TCZ exposure and could be associated with the underlying disease activity rather than the treatment (94). Safety data in pregnancy are limited and due to treatment-induced immunosuppression, an increased risk of maternal-feta l infections is theoretically possible in pregnant women treated with tocilizumab. In a systematic review assessing the benefits and safety of hyperimmune globulins to prevent HBV mother to child transmission in 2440 pregnant women, only one study mentioned adverse events consisting in swelling in two women (96). More recently, convalescent serum to treat the Ebola virus disease was evaluated in a non randomized comparative study of 99 patients which included eight pregnant women. No serious adverse reaction were associated with the transfusion (98). Two cases of pregnant women report the use of convalescent serum to treat SARS-CoV-2 infection (47,99). In the first case of a 31 years old pregnant woman, no serious adverse event related to the use of convalescent plasma was reported but its relative contribution to surviva l could not be determined due to other concomitant treatments. The authors concluded that its clinical benefit remained unknown (47). In the second case of a 35 year old pregnant woman with severe co morbidities who received both convalescent serum and remdesivir, no conclusion regarding safety or benefit of convalescent plasma could be drawn by the authors (99). Data on the use of specific hyper immunoglobulins to prevent infections in pregnant women seem reassuring as well as those on the use of convalescent serum although they are more scarce. If they proved to be effective in COVID-19 treatment, convalescent serum and specific hyper immunoglobulins directed against SARS-CoV-2 could be considered compatible with pregnancy in all trimesters. This article is protected by copyright. All rights reserved. (Table 2) Regarding potential asymptomatic infected pregnant women, the WHO recommends careful monitoring of patients with epidemiological history of contact with infected individuals, while The American College of Obstetricians and Gynecologists (ACOG) suggests routine antenatal care in this situation. An algorithm for assessment and management of symptomatic parturients has been proposed by ACOG, classifying them in three categories of risk: low, moderate and elevated. For mild presentations, women without comorbidities (low risk) should self-isolate at home, whereas those with health problems, obstetrical issues or the inability to care for themselves (moderate risk) should be seen in an ambulatory setting. According to The Royal College of Obstetricians and Gynaecologists (RCOG), pregnant women with moderate symptoms should self-isolate, unless they attend a maternity unit where patients in the 2 nd or 3 rd trimester meeting PHE criteria ( ≥ 1 of: (1) Clinical/radiological evidence of pneumonia, (2) Acute Respiratory Distress Syndrome (ARDS), (3) Fever ≥37.8 and at least one of acute persistent cough, hoarseness, nasal discharge/congestion, shortness of breath, sore throat, wheezing or sneezing) should be tested for COVID-19 and treated as infected until results are available. When pregnant women present with severe symptoms (high risk), they should immediately go to an emergency department according to ACOG algorithm. All guideline s agree that administration of corticosteroids for fetal lung maturity is still recommended per protocol for in the setting of a high risk of preterm birth when the mother's condition is stable. Regarding fetal growth surveillance, RCOG recommends an antenatal ultrasound fourteen days after acute illness resolution for hospitalized patients, while ACOG suggests a 3 rd trimester ultrasound for COVID-19 pregnant women infected in 2 nd and 3 rd trimester. A detailed anatomy ultrasound could be considered for 1 st trimester infections (ACOG). Data suggest that COVID-19 may be associated with an increased thromboembolic risk with a rate of venous thromboembolism (VTE) of 39% in ICU patients (100). Therefore, routine VTE Other coronavirus epidemics, such as SARS-CoV-1 had a higher impact on pregnant women encompassing 40% of ICU admissions and 12% of mortalities. The MERS-CoV epidemic was even more lethal with a 40% mortality without significant difference of severity between pregnant and non-pregnant women. In this review, we gathered more than 150 cases of SARS-CoV-2 in pregnancy and identified a maternal mortality of 2.7% (9 cases) among those described in the literature. ICU admissions were between 6.9% and 8%. The proportion of This article is protected by copyright. All rights reserved. severe complications seem to be equal to the non-pregnant population, however these must still be anticipated in pregnant women. These rates will have to be reviewed when the true denominator (number of infected pregnant women) is known, as a significant proportion of patients remain asymptomatic. Past coronavirus epidemics were associated with adverse outcomes for the fetus and/or newborns including miscarriages (57%), preterm birth, fetal distress and FGR with SARS-CoV-1 infection during the 2 nd and 3 rd trimesters. Also, MERS-CoV infection resulted in fetal and neonatal demise in 27% of cases. In this review, we found that of 142 cases of SARS-CoV-2 infections in pregnancy, 28% experienced preterm birth and 14% had adverse fetal/neonata l outcomes (FGR, fetal/neonatal demise, severe symptoms at birth). Potential mechanis ms include placental changes, as observed with SARS-CoV-1, and severe respiratory maternal illness, which could lead to placental insufficiency, IUGR and fetal distress/demise. The role of SARS-CoV-2 in early adverse pregnancy outcomes needs further investigation. With regards to pharmacological management, most agents currently tried are safe in pregnancy. As of April 22, 2020, prenatal management should be adapted to the patient's condition as indicated by ACOG and other algorithms (109). There is currently no agreement on specific prenatal ultrasound surveillance, but due to the potential risk of IUGR, it would seem reasonable to assess fetal growth surveillance during the third trimester of pregnancy. Administration of corticosteroids in pregnant women at risk of preterm birth should be administered per protocol, with consideration for the patient's condition. We recommend This article is protected by copyright. All rights reserved. considering parental preferences, the severity of illness and obstetrical indications when addressing the mode of delivery. Guidelines for pregnancy management will continue to be updated and professionals should stay informed about new guidelines. The acquisition of robust data on the impact of emergent pathogens on pregnant women is often lacking or only available after a considerable delay (4) This article is protected by copyright. All rights reserved. 102. COVID-19 and VTE-Anticoagulation -Hematology.org [Internet] . This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. Suspected perinatal Infection * 0 (0%) * 0/5 * (0%) 0/9 * (0%) 0 (0%) 1 (6%) 1/3 * (33%) * 0/6 * (0%) 3 (9%) 0 (0%) 0/10 * (0%) 0 (0%) 0 (0%) 2/10 * (20%) The nucleic acid test from the mother's amniotic fluid, vaginal secretions, cord blood, placenta, serum, anal swab, and breast milk were also negative. The most comprehensively tested case reported to date confirmed that the vertical transmission of COVID is unlikely. The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats. 9 Vlachodimitropoul ou Koumoutsea E, COVID19 and acute coagulopathy in pregnancy. Journal of thrombosis and haemostasis none The laboratory derangements may be reminiscent of HELLP syndrome, and thus knowledge of the COVID19 relationship is paramount for appropriate diagnosis and management. In addition to routine measurements of D-dimers, prothrombin time, and platelet count in all patients presenting with COVID19 as per ISTH guidance, monitoring of APTT and fibrinogen levels should be considered in pregnancy, as highlighted in this report. 10 Li L, [2] and their efforts to point out the error in Table 3 . After consideration of the information presented by Moradi et al., we have corrected the contents of Although vertical transmission of SARS-Cov2 has been excluded thus far and the outcome for mothers and fetuses has been generally good, the high rate of preterm cesarean delivery is a reason for concern. These interventions were typically elective, and it is reasonable to question whether they were warranted or not. In mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, PTB is the most common adverse pregnancy outcome. Miscarriage, preeclampsia, cesarean, and perinatal death (7-11%) were also more common than in the general population. It seems that the data in the second and third columns in Table 3 have been transposed, which needs correction. We present here the best evidence available to address many of these challenges, from making the diagnosis in symptomatic cases, to the debate between nucleic acid testing and chest imaging, to the management of the unwell patient in labor. This article is protected by copyright. All rights reserved. Khan S, Impact of COVID-19 infection on pregnancy outcomes and the risk of maternal-toneonatal intrapartum transmission of COVID-19 during natural birth. Infection control and hospital epidemiology 3 We report a case report study of 3 pregnant women with laboratory-confirmed COVID-19 pneumonia. All 3 pregnant women had vaginal deliveries. These patients presented with symptoms manifested by people with COVID-19.2 Of 3 patients, only 1 patient delivered a preterm baby. Saccone G, The novel coronavirus (2019-nCoV) in pregnancy: What we need to know. European journal of obstetrics, gynecology, and reproductive biology none In conclusion, strict monitoring of women with suspected 2019-nCoV is firmly recommended. Obstetricians should promptly recognize the symptoms of 2019-nCoV, and adequately assess severity and fetal well-being. With interest, we read the guidelines by Guillaume Favre and colleagues1 on the management of pregnant women with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we propose a translated algorithm for Spanish-speaking countries (appendix). We also suggest that the new breastfeeding recommendations and the option to use dexamethasone as an alternative to betamethasone are adopted in Latin America. This article is protected by copyright. All rights reserved. Khan S, Association of COVID-19 infection with pregnancy outcomes in healthcare workers and general women. Clinical microbiology and infection 17 In summary, we found two neonates suspected for COVID-19 infection and five neonates with neonatal pneumonia, suggesting the possibility that adverse pregnancy outcomes may be linked to COVID-19 infection. Shah PS, Classification system and case definition for SARS-CoV-2 infection in pregnant women, fetuses, and neonates. Acta obstetricia et gynecologica Scandinavica none At present the evidence for intrauterine transmission from mother to fetus or intrapartum transmission from mother to the neonate is sparse. There are limitations associated with sensitivity and specificity of diagnostic tests used and classification of patients based on test results has also been questioned. Deprest J, Feto-placental surgeries during the covid-19 pandemic: starting the discussion. Prenatal Diagnosis none Fetal diagnosis and pregnancy care need to be maintained, and we should strive to preotect the vulnerable population of pregnant women as well as their fetus, as much as possible. This includes both SARS-CoV2-negative and positive patients with fetal anomalies that may benefit from prenatal intervention. Mimouni F, Perinatal aspects on the covid-19 pandemic: a practical resource for perinatalneonatal specialists. Journal of Perinatalogy none Vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely. Consequences of COVID-19 infection among women during early pregnancy remain unknown. We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19. Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk. This article is protected by copyright. All rights reserved. Wilson AN, Caring for the carers: Ensuring the provision of quality maternity care during a global pandemic. Women and birth none This article provides an overview of important considerations for supporting the emotional, mental and physical health needs of maternity care providers in the context of the unprecedented crisis that COVID-19 presents. Cooperation, planning ahead and adequate availability of PPE is critical. Thinking about the needs of maternity providers to prevent stress and burnout is essential. Palatnik A, Protecting Labor and Delivery Personnel from COVID-19 during the Second Stage of Labor. American journal of perinatology none We recommend that labor and delivery personnel have the utmost caution and be granted the protection they need to protect themselves and other patients. This includes providing labor and delivery personnel full PPE including N95 for the second stage of labor. This is critical to ensure the adequate protection for health care workers and to prevent spread to other health care workers and patients. In summary, at present it must be stated that the general care recommendations that also apply to non-COVID-19 patients are initially valid with regard to obstetric anesthesia. Nevertheless, the special requirements on the part of hygiene and infection protection result in special circumstances that should be taken into account when caring for pregnant patients from an anesthetic point of view. McIntosh JJ, Corticosteroid Guidance for Pregnancy during COVID-19 Pandemic. American journal of perinatology none It is necessary that obstetricians adjust practice to carefully weigh the fetal benefits with maternal risks. Therefore, our institution has examined the risks and benefits and altered our corticosteroid recommendations. Gonzalez-Brown VM, Operating Room Guide for Confirmed or Suspected COVID- 19 Pregnant Patients Requiring Cesarean Delivery. American journal of perinatology none This is a suggested protocol which may not be applicable to all health care settings but can be adapted to local resources and limitations of individual L&D units. This article is protected by copyright. All rights reserved. Parazzini F, Delivery in pregnant women infected with SARS-CoV-2: A fast review. International journal of gynaecology and obstetrics 64 The rate of vertical or peripartum transmission of SARS-CoV-2 is low, if any, for cesarean delivery; no data are available for vaginal delivery. Low frequency of spontaneous preterm birth and general favorable immediate neonatal outcome are reassuring. Huang X, Epidemiology and Clinical Characteristics of COVID-19. Archives of Iranian medicine none The basic strategy for controlling the epidemic is early detection, early isolation, early diagnosis and early treatment. COVID-19 cases are insidious and transmissible in the incubation period, and multiple clusters have been reported in China. The causal role of COVID-19 in these cases is therefore uncertain and larger studies are needed in the future to describe the prevalence, clinical characteristics and course of the disease. Pérez-López FR, Severe acute respiratory syndrome coronavirus 19 and human pregnancy. Gynecological endocrinology none Outcomes of pregnants delivering in the upcoming months will provide more information on this particular new disease and its relation to pregnancy. In the meantime, it seems best that women should be encouraged to delay becoming pregnant until more evidence related to risks associated to COVID-19 infection during pregnancy is available. In addition, women susceptible to be submitted to assisted reproductive technology should take some additional precautions as recently recommended by La Marca et al. Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and child care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child. The manuscript outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother, including three optional variations of current standards involving shared-decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and postdischarge care. The availability of resources may also drive the application of these guidelines. This article is protected by copyright. All rights reserved. Bourne Lancet . Infectious diseases 7 The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of nonpregnant adults with COVID-19 that have been reported in the literature. Given that 420 patients were diagnosed by Mar. 11th in Shenzhen and tens of cases was diagnosed in our hospital, yet no nosocomial infection has occurred and none of the pregnant woman registered in our hospital was reported to be infected, this management should be effective to an extant, however mathematical model may be needed to quantify the effectiveness of these methods. On January 28, we published "Guidance for maternal and fetal management during pneumonia epidemics of novel coronavirus infection in the Wuhan Tongji Hospital (First edition)" [4] . Based on the clinical characteristics, diagnosis and treatment progress of the recently discovered diseases, we offered an updated clinical management for pregnant women and newborns with NCP. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. We therefore updated the guidelines according to the data available at the beginning of March, 2020 (appendix). It is our responsibility, as specialists working in different fields of perinatology, to improve our own recommendations and that of others for the benefit of our patients. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet A Novel Coronavirus from Patients with Pneumonia in China Zika Virus Infection -After the Pandemic SARS and MERS: recent insights into emerging coronaviruses Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 First experience of COVID-19 screening of health-care workers in England. The Lancet WHO | Summary table of SARS cases by country This article is protected by copyright. All rights reserved WHO | Middle East respiratory syndrome coronavirus (MERS-CoV) Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Coronavirus Disease 2019 (COVID-19) and Pregnancy: What obstetricians need to know Guillain-Barré syndrome related to COVID-19 infection Presumed Asymptomatic Carrier Transmission of COVID-19 A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet Real estimates of mortality following COVID-19 infection Authors' reply. The Lancet Infectious Diseases Estimates of the severity of coronavirus disease 2019: a model-based analysis. The Lancet Infectious Diseases Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy Clinical characteristics and records. The Lancet Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan Coronavirus Disease in China Mothers With COVID-19 Pneumonia Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn Available from: This article is protected by copyright. All rights reserved Can SARS-CoV-2 Infection Be Acquired In Utero?: More Definitive Evidence Is Needed Preterm delivery in pregnant woman with critical COVID-19 pneumonia and vertical transmission Profound childhood deafness. Inner ear pathology Ototoxicity of Chloroquine Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding Use of hydroxychloroquine during pregnancy and breastfeeding: An update for the recent coronavirus pandemic (COVID-19) Drugs in Pregnancy and Lactation Drugs During Pregnancy and Lactation -3rd Edition Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings Safety and efficacy of Society of Critical Care Medicine (SCCM) Should we stop aspirin prophylaxis in pregnant women diagnosed with COVID-19? Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection during pregnancy: Report of two cases & review of the literature Middle East Respiratory Syndrome Coronavirus Infection During Pregnancy: A Report of 5 Cases From Saudi Arabia Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. The Lancet Infectious Diseases Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy Clinical Features and Outcomes of Pregnant Women Suspected of Coronavirus Disease Perinatal Transmission of COVID-19 Associated SARS-CoV-2: Should We Worry? A case report of neonatal COVID-19 infection in China A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery COVID-19 in pregnancy with comorbidities: More liberal testing strategy is needed An Uncomplicated Delivery in a Patient with Covid-19 in the United States Emergency cesarean section on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed patient COVID-19), Practice Advisory. The American College of Obstetricians and Gynecologists COVID-19) Infection in Pregnancy, Information for healthcare professionals Version 7. Royal College of Obstetricians & Gynaecologists COVID-19 -guidance for neonatal settings. Royal College of Paediatrics and Child Health Current criteria PHE criteria(correct at the time of publishing this update) are: Women who are being/are admitted to hospital with one of the following: • Clinical/radiological evidence of pneumonia, • Acute Respiratory Distress Syndrome (ARDS), • Fever ≥37.8 AND at least one of acute persistent cough, hoarseness, nasal discharge/congestion, shortness of breath National Institute for Health and Care Excellence This article is protected by copyright. All rights reserved.Accepted Article This article is protected by copyright. All rights reserved. This article is protected by copyright. All Ten key recommendations were provided for the management of COVID-19 infections in pregnancy.This article is protected by copyright. All rights reserved.Accepted Article 92 Zhou D, COVID-19: a recommendation to examine the effect of hydroxychloroquin e in preventing infection and progression.Review article The Journal of antimicrobial chemotherapy none In summary, we propose that hydroxychloroquine (HCQ) could serve as a better therapeutic approach than chloroquine (CQ) for the treatment of SARS-CoV-2 infection. There are three major reasons for this: (i) HCQ is likely to attenuate the severe progression of COVID-19 through inhibiting the cytokine storm by reducing CD154 expression in T cells; (ii) HCQ may confer a similar antiviral effect at both pre-and post-infection stages, as found with CQ; (iii) HCQ has fewer side effects, is safe in pregnancy and is cheaper and more highly available in China. If there is an indication for obstetric surgery or critical illness of COVID-19 in pregnant women, timely termination of pregnancy will not increase the risk of premature birth and asphyxia of the newborn, but it is beneficial to the treatment and rehabilitation of maternal pneumonia. Preventive use of long-acting uterotonic agents could reduce the incidence of postpartum hemorrhage during surgery. 2019-nCoV infection has not been found in neonates deliverd from pregnant women with COVID-19. Journal of infection 13 The report showed pregnant women are also susceptible to SARS-CoV-2 infection. SARS-CoV-2 may increase health risks to both mothers and infants during pregnancy. Efforts should be taken to reduce the infection rate of SARS-CoV-2 both in pregnant and perinatal period, and more intensive attention should be paid to pregnant patients. Review article International nursing review none The next decade is likely to produce any number of global challenges that will affect health and health care, including pan-national infections such as the new coronavirus COVID-19 and others that will be related to global warming. Nurses will be required to react to these events, even though they will also be affected as ordinary citizens. The future resilience of healthcare services will depend on having sufficient numbers of nurses who are adequately resourced to face the coming challenges. none NOT ABOUT CORONAVIRUS -2 Therefore, P100C4 potentially could be tested as a priming vaccine or be further modified using reverse genetics. It also can be administered in multiple doses or be combined with inactivated or subunit vaccines and adjuvants as a PEDV vaccination regimen, whose efficacy can be tested in the future.This article is protected by copyright. All rights reserved. NOT ABOUT CORONAVIRUS -2 MERS-CoV remains an uncommon disease among children, and its course follows a milder path among children than those of adults. Majority of cases were asymptomatic and were diagnosed during the course of contact investigation. NOT ABOUT CORONAVIRUS -2 IFN-based drugs enhance the protective effect of vaccination against associative infections in the newborn calves. They stimulate a rise in the titer of antibodies to Rotavirus, coronavirus, VD, and mucosal disease complex as well as an increase in immunoglobulins A, M, and G.