Expert Review ajog.org

Coronavirus Disease 2019 (COVID-19) andpregnancy: what obstetricians need to know

Sonja A. Rasmussen, MD, MS; John C. Smulian, MD, MPH; John A. Lednicky, PhD; Tony S. Wen, MD;Denise J. Jamieson, MD, MPH

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From the Departments of Pediatrics (Dr Rasmussen) andObstetrics andGynecology (Drs Smulian andWen), University of FloridaCollege ofMedicine, theDepartment of Epidemiology (Dr Rasmussen), University of Florida College of Public Health and Health Professions and College of Medicine, and theDepartment of Environmental and Global Health, University of Florida College of Public Health and Health Professions, and University of Florida EmergingPathogens Institute (Dr Lednicky), Gainesville, FL; and the Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA(Dr Jamieson).

Received Feb. 12, 2020; revised Feb. 17, 2020; accepted Feb. 18, 2020.

The authors report no conflict of interest.

Corresponding author: Sonja A. Rasmussen, MD, MS. skr9@ufl.edu

0002-9378/$36.00 � ª 2020 Elsevier Inc. All rights reserved. � https://doi.org/10.1016/j.ajog.2020.02.017

Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, inDecember 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associatedwith other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provideinsights into coronavirus disease 2019’s effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold tosevere respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel frommainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest anincubation period ofw5 days (range, 2e14 days). Average age of hospitalized patients has been 49e56 years, with a third to half with anunderlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54e73%). Frequent manifes-tations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging,lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17e29% ofhospitalized patients. Overall case fatality rate appears to bew1%; however, early datamay overestimate this rate. In 2 reports describing 18pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnantadults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of inutero transmission was seen.

Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratorysyndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanicalventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended inspontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle Eastrespiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contactinvestigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmissionwas seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have beenapproved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications,management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirusdisease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload,consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterinecontraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-basedapproach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue tofollow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).

Key words: fetal death, fetus, maternal death, Middle East respiratory syndrome, newborn, novel coronavirus, 2019 novel coronavirus,perinatal infection, pneumonia, pregnancy, preterm birth, severe acute respiratory syndrome, severe acute respiratory syndromecoronavirus 2, vertical transmission

MONTH 2020 American Journal of Obstetrics & Gynecology 1

Expert Review ajog.org

merging infections have been

E shown to have an important impacton pregnant women and their fetuses,1

with the increased risk of complicationsin pregnant women with the 2009pandemicH1N1 influenza virus2 and thesevere fetal effects of Zika virus as recentexamples.3,4 The emergence of a coro-navirus not previously seen in humans,first reported in Wuhan, China, on Dec.31, 2019, has attracted much interestthroughout the world. Since then, thenumber of reported cases has increasedrapidly, with more than 51,800laboratory-confirmed cases and 1600deaths as of Feb. 16, 2020.

In addition to China, cases havespread to 25 other countries (Figure 1)including 15 cases in the United States.Initial outbreak data from China show anear exponential growth of reportedcases.5 Reported numbers are likely un-derestimates of the true numbersbecause milder cases are less likely to bereported.

On Jan. 30, 2020, the World HealthOrganization declared the outbreak as apublic health emergency of internationalconcern; on Jan. 31, 2020, the UnitedStates declared a public health emer-gency, and the Centers for DiseaseControl and Prevention issued a federalquarantine for 195 Americans who

GLOSSARY OF TERMS

� 2019-nCoV: 2019-novel coronavirus (prev� Basic reproduction number: estimate of num

from a single person in a population in wh� CDC: US Centers for Disease Control and P� COVID-19: coronavirus disease 2019 (prev

nCoV]; illness caused by SARS-CoV-2.� MERS: Middle East respiratory syndrome.� MERS-CoV: Middle East respiratory syndr

East respiratory syndrome (MERS).� N95 respirator: respiratory protective devic

(0.3 mm) test particles; also called N95 filt� SARS: severe acute respiratory syndrome.� SARS-CoV: severe acute respiratory syndr

acute respiratory syndrome (SARS).� SARS-CoV-2: severe acute respiratory syn

the novel coronavirus, according to the Inruses), virus that causes COVID-19.

� WHO: World Health Organization.

2 American Journal of Obstetrics & Gynecology M

traveled from Wuhan, China, its firstfederal quarantine inmore than 50 years.On Feb. 11, the new coronavirus dis-

ease (previously referred to as 2019 novelcoronavirus (2019-nCoV)) received anofficial name from the World HealthOrganization (WHO), CoronavirusDisease 19 (COVID-19) (Figure 2).6 TheInternational Committee on Taxonomyof Viruses has proposed severe acuterespiratory syndrome coronavirus 2(SARS-CoV-2) as the name of the virusthat causes COVID-19.7

Coronaviruses are single-strandedRNA, nonsegmented, enveloped vi-ruses, which cause illness ranging inseverity from the common cold to severeand fatal illness. The term coronavirusderives from the Latin word corona,which means crown or halo; that desig-nation arises from the appearance ofcoronavirus virions viewed by electronmicroscopy, in which the virus particlesdisplay a crown-like fringe typicallyreferred to as spikes (Figure 3).In the past 2 decades, 2 other coro-

naviruses that cause severe respiratoryillness in humans have emerged: severeacute respiratory syndrome coronavirus(SARS-CoV) and the Middle East res-piratory syndrome coronavirus (MERS-CoV). With the emergence of SARS-CoV-2, a third coronavirus that can

ious name for COVID-19 and SARS-CoV-2).ber of individuals who will become infectedich all individuals are susceptible.revention.iously called 2019 novel coronavirus [2019-

ome coronavirus, virus that causes Middle

e that removes at least 95% of very smallering facepiece respirator.

ome coronavirus, virus that caused severe

drome coronavirus 2 virus (current name ofternational Committee on Taxonomy of Vi-

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cause severe respiratory illness has beenidentified. In a short period of time, thisnovel coronavirus has caused more casesof illness than were reported for MERSand SARS combined.

Here we summarize what is currentlyknown about COVID-19 and what thismeans for practicing obstetricians andtheir pregnant patients. Because so littleis currently known about COVID-19 inpregnancy, we also review available in-formation on the effects of SARS andMERS during pregnancy to inform careof pregnant women with COVID-19until additional data on pregnantwomen and their fetuses becomeavailable.

SARS and its effects on pregnantwomenSevere acute respiratory syndrome(SARS) is caused by the SARS-CoV. Re-ports of the emergence of SARS-CoVappeared in February 2003, with thefirst cases observed in GuangdongProvince in China. The virus spread tonearly 30 countries throughout theworld, resulting in more than 8000 casesand 770 deaths.8

The outbreak was brought undercontrol after public health control mea-sures to reduce contact with infectedpersons were put into place, and no caseshave been seen since 2004. Manifesta-tions of SARS consist of fever, chills,headache, malaise, and myalgia. Diar-rhea was seen in some patients. Pneu-monia was nearly always seen in patientsdiagnosed with SARS, with mechanicalventilation being required in 10e20% ofcases. Case fatality rate was estimated at9e10% (Table).

The natural reservoir for SARS-CoV isbelieved to be bats; however, some evi-dence supported civet cats or raccoondogs as possible intermediate sources ofthese illnesses.8 SARS is transmitted byclose person-to-person contact throughcontact of the mucus membranes of therespiratory tract with respiratory drop-lets formed when an infected personcoughs or sneezes. Fecal-oral trans-mission and transmission via fomiteshave also been reported.8 Airbornespread because of inhalation of smallparticle aerosols may also be possible.

FIGURE 1Global map of confirmed COVID-19 cases

Global map of confirmed COVID-19 cases (as of Feb. 14, 2020) (from https://www.cdc.gov/

coronavirus/2019-ncov/locations-confirmed-cases.html).

COVID-19, coronavirus disease 2019.

Rasmussen. 2019 novel coronavirus and pregnancy. Am J Obstet Gynecol 2020.

ajog.org Expert Review

Transmission in health care settingswas frequently seen during the 2003outbreak, with superspreading (when asingle patient transmits infection to adisproportionate number of contacts)reported.9 The incubation period wasestimated at a mean of 4.6 days, with arange of 2e14 days. Transmissionappeared to occur most often during thesecond week of illness when viral excre-tion is highest; there is no evidence that aperson with SARS is contagious beforesymptom onset.

The largest case series of pregnantwomen with SARS was from the 2003outbreak in Hong Kong, in which 12pregnant women were identified.10 Thecase-fatality rate was 25% (3 deaths).Clinical and laboratory findings weresimilar to those seen in the nonpregnantpopulation. Pneumonia on chest radio-graph or computed tomography wasseen in all patients. Major medicalcomplications included adult respiratorydistress syndrome in 4, disseminatedintravascular coagulopathy (DIC) in 3,renal failure in 3, secondary bacterialpneumonia in 2, and sepsis in 2 patients.

Pregnancy outcomes varied bytrimester of presentation.10 Among the 7women who became ill in the firsttrimester, 4 had a spontaneous abortion,2 had pregnancy terminations for socialreasons after recovery from SARS, and 1delivered a full-term healthy infant.Among the 5 women who presented af-ter 24 weeks’ gestation, 4 delivered pre-term. Three women delivered bycesarean delivery because of deterio-rating maternal condition from theirSARS illness at 26, 28, and 32 weeks’gestation.11 These babies had birth-weights appropriate for gestational age.Two of the infants had respiratorydistress syndrome requiring surfactant(born at 26 and 28 weeks’ gestation),with one later developing broncho-pulmonary dysplasia.

Gastrointestinal complications wereobserved in 2 infants, including a jejunalperforation in an infant delivered at 26weeks and necrotizing enterocolitis withileal perforation in an infant delivered at28 weeks’ gestation. Whether thesegastrointestinal complications wererelated to complications from SARS or

its treatment or whether they were sec-ondary to preterm delivery is un-known.11 The two infants who weredelivered after their mothers’ recoveryfrom SARS had intrauterine growth re-striction. No clinical, radiologic, or lab-oratory evidence for transmission frommother to fetus was observed, despitelaboratory testing of differentspecimens.12,13

A matched case-control study14

compared 10 of the 12 pregnantwomen noted in the previous text (2were excluded because they were unableto be matched) with 40 nonpregnantwomen with SARS. Women werematched on sex, age, timing of con-tracting SARS, health care worker status,underlying illness, and whether thewoman resided in a housing area inwhich there was a large outbreak.Pregnancy appeared to have no effect

on clinical symptoms or time to pre-sentation after symptom onset. Howev-er, complications and adverse outcomeswere more common among pregnantwomen: women who were pregnant hada longer hospital stay, were statisticallysignificantly more likely to develop renalfailure, sepsis, and DIC, and were morelikely to require intensive care unitadmission. Forty percent of pregnantwomen required mechanical ventilation,

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compared with 13% of nonpregnantpatients (P¼.07). Pregnant womenwerealso significantly more likely to die (P ¼.01).

We identified 5 reports of additionalcases of SARS during pregnancy treatedin Hong Kong (n ¼ 2), the United States(n¼ 2), and Canada (n¼ 1).15e19 Two ofthe 5 women required mechanical venti-lation, 1 required hemodialysis for acuterenal failure, and 1 had seizures andpositive cerebrospinal fluid for SARS-CoV, suggestive of a central nervous sys-tem infection. All patients recovered fromtheir illness. In 1 case, the pregnancy wasterminated at the mother’s request; theremaining pregnancies ended in liveborninfants (2 at term and 2 preterm). Testingof neonatal specimens for SARS-CoVRNAwas negative.

Several hospitals in Toronto and HongKong reported measures instituted onobstetrics services during the SARSoutbreak to decrease transmission topregnant women, their families, com-munity members, and health careworkers.20,21 For example, all hospitalstaff, patients, and visitors were screenedfor symptoms at the hospital entranceand wore N95 respirators. Visitors werelimited to 1 per patient on labor anddelivery, with no visitors allowed in thepostpartum ward.

American Journal of Obstetrics & Gynecology 3

FIGURE 2Timeline showing key events in the COVID-19 outbreak

Dec 1, 2019 1st case of

pneumonia of unknown

cause (later iden�fied as COVID-19)

recognized in Wuhan, China

Dec 31, 2019 China no�fies

WHO of pneumonia outbreak in

Wuhan

Jan 7, 2020Chinese

scien�sts iden�fy new coronavirus

Jan 9, 2020 China shares

gene�c sequence of

novel coronavirus

Jan 13, 20201st case

iden�fied outside of China in Thailand

Jan 17, 2020US CDC

ins�tutes health screening at

three airports

Jan 21, 2020 1st case

confirmed in US, US CDC ac�vates its Emergency Opera�ons

Center

Feb 2, 2020 US State

Department recommends people avoid

travel to China

Jan 30, 2020 WHO declares Public Health Emergency of Interna�onal

Concern, 1st case of human-to-human transmission in US

Jan 31, 2020 US CDC orders quaran�ne of

people arriving from Hubei

province, US declares public

health emergency

Feb 11, 2020Illness caused

by novel coronavirus

receives official name from WHO: COVID-19

December 2019 January 2020 February 2020

Timeline showing key events in the COVID-19 outbreak, Dec. 1, 2019, through Feb. 15, 2020.

CDC, Centers for Disease Control and Prevention; COVID-19, coronavirus disease 2019; US, United States; WHO, World Health Organization.

Rasmussen. 2019 novel coronavirus and pregnancy. Am J Obstet Gynecol 2020.

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Postpartum stays were reduced inlength with a postpartum nurse homevisit added. Postpartum patients wereasked to observe a 10 day home quar-antine. Health care workers were askedto observe a work quarantine in whichthey were asked to go directly fromhometo work and vice versa to minimizeinteraction in the community. Obstetricservices considered to be nonessentialsuch as routine ultrasound and prenataldiagnosis were suspended. Although theimpact of these interventions was notevaluated, there may be some relevantlessons learned from these experiencesduring SARS that could help inform theapproach to COVID-19.

MERS and its effects on pregnantwomenMiddle East Respiratory Syndrome(MERS) is a respiratory illness caused byMERS-CoV. The illness was first identi-fied in Saudi Arabia in 2012, with spread

4 American Journal of Obstetrics & Gynecology M

to other countries in the Arabianpeninsula and eventually to countriesoutside the Arabian peninsula, includingthe United States.22,23 The largestoutbreak outside the Arabian Peninsulawas in the Republic of Korea in 2015.Nearly 2500 cases of MERS-CoV

illness and more than 860 deaths havebeen reported with continuing reportsinto the present. The manifestations ofMERS include severe respiratory illnesscharacterized by fever, cough, andshortness of breath. Some patients alsohave diarrhea. The case fatality rate isestimated to be 35e40%.Patients who developed MERS were

more likely to be older (median age is50 years) with about two thirds ofpatients being male. Patients withMERS were also more likely to have anunderlying illness. Some patients withMERS-CoV infection have been asymp-tomatic (identified through contactinvestigations).

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The mean incubation period is 5.2days, with a range of 2e13 days. As withSARS, MERS is mainly spread person toperson through close contact, withtransmission in health care settings, andsuperspreading events have beenobserved. However, since 2016, thenumber of cases of MERS-CoV has beendramatically reduced after public healthefforts to prevent MERS-CoV trans-mission were put into place.24

Information on MERS among preg-nant women is limited. We identifiedreports of 13 cases of pregnant womenwith MERS from several countries,including Saudi Arabia (n ¼ 8), Korea(n ¼ 2), Jordan (n ¼ 1), United ArabEmirates (n ¼ 1), and Philippines (n ¼1).13,25e31 Two women were asymp-tomatic, identified as part of a contactinvestigation. Among the 11 symptom-atic women, manifestations were similarto those seen in nonpregnant patientswith MERS.

FIGURE 3Illustration of the causative virion for COVID-19

Reproduced, with permission, from the Centers for Disease Control and Prevention/Alissa Eckert, MS

(obtained from the CDC’s Public Health Image Library; https://phil.cdc.gov/Details.aspx?

pid=23312).

COVID-19, coronavirus disease 2019.

Rasmussen. 2019 novel coronavirus and pregnancy. Am J Obstet Gynecol 2020.

ajog.org Expert Review

Seven of 13 patients were admitted toan intensive care unit for respiratorydeterioration or acute respiratorydistress syndrome, 5 required ventilatorsupport, 3 died, and 8 recovered. Amongthe 3 deaths, themothers died 8e25 daysafter delivery. Both babies born toasymptomatic womenwere born healthyat term; among those who were symp-tomatic, there was 1 intrauterine fetaldemise, 1 stillbirth, 1 baby delivered at 25weeks who died 4 hours after birth, 2healthy preterm infants, and 5 healthyterm infants (infant status was notmentioned for 1).

Coronavirus disease 2019 (COVID-19)Clinical, epidemiologic, and viralcharacteristics. Respiratory illnesscaused by a novel coronavirus (nowreferred to as SARS-CoV-2) was firstnoted in December 2019 in Wuhan,Hubei Province, China. The WHOChina Country office was notified of anoutbreak of pneumonia of unknownetiology on Dec. 31, 2019 (Figure 2).Between Dec. 31, 2019, and Jan. 3,2020, 44 cases were reported to theWHO. On Jan. 7, 2020, Chineseauthorities identified a novelcoronavirus as the cause. The virus hasquickly spread first through Wuhanand subsequently to other areas ofChina and other countries in the world(Figure 1).

Early data suggested an associationbetween the Huanan Seafood WholesaleMarket and COVID-19 with 27 of 41cases in 1 report32 and 26 of 47 inanother report33 with epidemiologiclinks to the market, leading to closure ofthe market on Jan. 1, 2020. Given thatthe earliest case reported (illness onseton Dec. 1, 2019)32 did not have exposureto the market raises the possibility thatthe initial emergence into humansoccurred elsewhere. However, samplingof the market’s environment supportsthe market’s importance in early trans-mission of the virus. Later cases weremuch less likely to have visited themarket, supporting the role of person-to-person transmission in later cases.

The SARS-CoV-2 is a betacoronavirussimilar to SARS-CoV and MERS-CoV(Table). Sequencing data show that the

SARS-CoV-2 is most closely related tocoronaviruses found in bats, with morethan 85% nucleotide identity with a batSARS-like CoV.34,35 The virus has 79%nucleotide identity to SARS-CoV andabout 50% to MERS-CoV.35

Bats appear to be the natural reservoirsof both SARS-CoVand MERS-CoV. Theemergence of these viruses in humanshas been attributed to host switching: thevirus jumped from an intermediary hostspecies (eg, civet cats for SARS-CoV anddromedary camels for MERS-CoV) tohumans. An intermediary host species isthought to be likely for SARS-CoV-2,35

although it has been yet to be identified.Sequence data show a high degree(>99.98%) of similarity of the virusamong different patients, suggesting arecent emergence in humans.Clinical manifestations of COVID-19

are similar to those with SARS andMERS (Table). Studies of hospitalizedpatients with COVID-19 show that pa-tients commonly develop severe pneu-monia, with 23e32% admitted to the

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intensive care unit and 17e29% of casesprogressing to acute respiratory distresssyndrome. 32,36,37 Among hospitalizedpatients, 4e15% have died.32,36,37

Overall case fatality ratio estimates(including asymptomatic and symp-tomatic infections) appear to be in therange of 1% (95% confidence interval,0.5e4%),38 although these estimatesshould be considered preliminary.

Average age of hospitalized patientswas 49e56 years, with 32e51% havingan underlying illness. Most patients(54e73%) were men. Children withCOVID-19 appear to be rarely identi-fied, with only 28 children reported as ofJan. 30, 2020 (<1%of total), andmost ofthose identified had mild symptoms.39

No pregnant women were reported inany of these initial cohorts. Commonmanifestations among hospitalized pa-tients were fever (83e100%), cough(59e82%), myalgia (11e35%), head-ache (7e8%), and diarrhea (2e10%).All patients had abnormalities onradiographic imaging of the chest.

American Journal of Obstetrics & Gynecology 5

TABLEComparison of characteristics of SARS, MERS, and COVID-19a

Characteristics SARS MERS COVID-19

First patients reported Guangdong, China, November 2002 Zarga, Jordan, April 2012, andJeddah, Saudi Arabia, June 2012

Wuhan, China, December 2019

Virus SARS-CoV MERS-CoV SARS-CoV-2

Type of coronavirus Betacoronavirus Betacoronavirus Betacoronavirus

Host cell receptor Angiotensin converting enzyme 2 Dipeptidyl peptidase 4 Structural analysis suggests angiotensin convertingenzyme 2 receptor52

Sequence similarity Reference 79% to SARS-CoV, 50% to MERS-CoV35

Animal hosts Bats (natural reservoir), masked palm civet andraccoon dogs may be intermediate hosts

Bats (natural reservoir), dromedarycamel (intermediate host)

Bats, animals sold at the seafood market in Wuhan mightrepresent an intermediate host35

Incubation period

Mean (95% CI, d) 4.6 (3.8e5.8) 5.2 (1.9e14.7) 5.2 days (95% confidence interval [CI], 4.1e7.0); 95thpercentile of the distribution was 12.5 days33

Range, d 2e14 2e13 2e14

Time from illness onset untilhospitalization

2e8 days 0e16 days 12.5 days (mean) (95% CI, 10.3e14.8), onset beforeJan. 19.1 days (mean); 95% CI, 8.6e9.7 (onset Jan. 1e11)33

Basic reproduction number (R0)b 2e3 <1 2.2 (95% CI, 1.4e3.9)33

Patient characteristics

Adults 93% 98% Nearly all reported patients are adults

Children 5e7% 2% Children have been infrequently reported (<1% of cases)39

Age range, y 1e91 1e94 10e89 y

Average age, y Mean, 39.9 Median, 50 59 years (median)33

Sex ratio (M:F) 43%:57% 64.5%:35.5% 56%:44%33

Mortality

Case fatality rate overall 9.6% 35e40% Initial estimate is 1%38

Rasmussen. 2019 novel coronavirus and pregnancy. Am J Obstet Gynecol 2020. (continued)

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TABLE

Com

parisonof

characteristicsof

SARS,M

ERS,and

COVID-19a

(continued)

Characteristics

SARS

MER

SCOVID-19

Clinicalmanifestations

From

hospitalized

patients3

2,36,37

Fever

99e100%

98%

83e100%

Cough

62e100%

83%

59e82%

Myalgia

45e61%

32%

11e35%

Headache

20e56%

11%

7e8%

Diarrhea

20e25%

26%

2e10%

Laboratoryfindings

Radiographicabnorm

alities

onchestimaging

94e100%

90e100%

100%

Leukopenia

25e35%

14%

9e25%

Lymphopenia

65e85%

32%

35e70%

Thrombocytopenia

40e45%

36%

5e12%

COVID-19,coronavirusdisease2019;M

ERS,M

iddleEastrespiratorysyndrome;MERS-CoV,M

iddleEastrespiratorysyndromecoronavirus;SARS,severeacuterespiratorysyndrome;SARS-CoV,severeacuterespiratorysyndromecoronavirus;SARS-CoV-2,severe

acuterespiratorysyndromecoronavirus2.

aModified

from

Rasmussenetal23;bBasicreproductionnumber,defined

asaveragenumberofpeoplewho

willbecomeinfected

from

asingleinfected

person.

Rasmussen.

2019

novelcoronavirus

andpregnancy.Am

JObstetGynecol2020.

ajog.org Expert Review

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Person-to-person transmission ofSARS-CoV-2 is thought to be similar totransmission of influenza and otherrespiratory pathogens; respiratorydroplets are formed when an infectedperson coughs or sneezes and thesedroplets are inhaled by close contacts,generally within 6 feet. It is unclearwhether infection can be transmittedfrom fomites. Fecal-oral transmissionmight be possible, given that SARS-CoV-2 has been identified in stool speci-mens40 and SARS-CoV might have beentransmitted in this manner.41

The basic reproduction number, R0(the average number of people who willbecome infected from a single infectedperson in a population in which allpersons are susceptible) is affected byfactors such as the duration of infectivity,the transmissibility of the pathogen, andthe number of susceptible contacts.Measles, which is highly infective, has anR0 of 12e18, while 2009 H1N1 influ-enza and SARS have an R0 of 1.2e1.6and 2e5, respectively.42 Current esti-mates of R0 for SARS-CoV-2 places it at2.2 (95% confidence interval, 1.4e3.9)33

As with SARS and MERS, nosocomialtransmission is playing a key role intransmission, presumed to be respon-sible for infection of 29% of affectedhealth professionals and 12% of hospi-talized patients in a recent study.37

Implications of COVID-19 forpregnant womenIn the midst of a rapidly evolvingoutbreak that could have significant ef-fects on our public health and medicalinfrastructure, the unique needs ofpregnant women should be included inpreparedness and response plans. Inprevious outbreaks, clinicians have attimes been reluctant to treat or vaccinatepregnant women because of concerns forfetal safety.43 It is critical that pregnantwomen not be denied potentially life-saving interventions in the context of aserious infectious disease threat unlessthere is a compelling reason to excludethem. As with all decisions regardingtreatment during pregnancy, carefullyweighing of the benefits of interventionsfor the mother and fetus with potentialrisks is necessary. As surveillance systems

American Journal of Obstetrics & Gynecology 7

BOX 1Criteria to guide evaluation of persons under investigation for COVID-19

Clinical features AND Epidemiologic risk

Fevera or signs/symptoms of lower respiratory illness(eg, cough or shortness of breath)

AND Any person, including health care workers, who hashad close contactb with a laboratory-confirmed COVID-19 patient within 14 days of symptom onset

Fevera and signs/symptoms of a lower respiratoryillness (eg, cough or shortness of breath)

AND A history of travel from Hubei Province, China, within14 days of symptom onset

Fevera and signs/symptoms of a lower respiratoryillness (eg, cough or shortness of breath) requiringhospitalization

AND A history of travel from mainland China within 14 daysof symptom onset

The criteria are intended to serve as guidance for evaluation. Patients should be evaluated and discussed with public health departments on a case-by-case basis if their clinical presentation orexposure history is equivocal (eg, uncertain travel or exposure) (see https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html for updates).

COVID-19, coronavirus disease 2019.

a Fever may be subjective or confirmed; b Close contact is defined as follows: (1) being within w6 feet (2 m) of a COVID-19 case for a prolonged period of time while not wearing recommendedpersonal protective equipment (eg, gowns, gloves, NIOSH-certified disposable N95 respirator, eye protection); close contact can occur while caring for, living with, visiting, or sharing a health carewaiting area or room with a COVID-19 case; OR (2) having direct contact with infectious secretions of a COVID-19 case (eg, being coughed on) while not wearing recommended personal protectiveequipment.

Rasmussen. 2019 novel coronavirus and pregnancy. Am J Obstet Gynecol 2020.

Expert Review ajog.org

for cases of COVID-19 are established, itis essential that information on preg-nancy status, as well asmaternal and fetaloutcomes, be collected and reported.

Susceptibility to and severity ofCOVID-19 in pregnancy. Althoughdata are limited, there is no evidencefrom other severe coronavirus infections(SARS or MERS) that pregnant womenare more susceptible to infection withcoronavirus. Thus far, in this outbreak ofnovel coronavirus infection, more menhave been affected than women.32,33,36,37

This observed gender difference could bedue to differences in reporting,susceptibility, exposure, or recognitionand diagnosis of infection. There are nodata to inform whether pregnancyincreases susceptibility to COVID-19.

Previous data on SARS and MERSsuggest that clinical findings duringpregnancy can range from no symptomsto severe disease and death. The mostcommon symptoms of COVID-19 arefever and cough, with more than 80% ofhospitalized patients presenting withthese symptoms.36

In a recent study by Chen et al,44 9women diagnosed with COVID-19during the third trimester of pregnancywere reported. In this small series, clin-ical presentation was similar to that seenin nonpregnant adults, with fever in 7,

8 American Journal of Obstetrics & Gynecology M

cough in 4, myalgia in 3, and sore throatand malaise each in 2 women. Five hadlymphopenia. All had pneumonia, butnone required mechanical ventilation,and none died. All women had a cesar-ean delivery, and Apgar scores were 8e9at 1 minute and 9e10 at 5 minutes.In a second series of 9 pregnancies

with 10 infants (1 set of twins) reportedby Zhu et al.,45 symptom onset wasbefore delivery (1e6 days) in 4, on theday of delivery in 2, and after delivery(1e3 days) in 3 cases. Clinical presen-tation of COVID-19 was similar to thatseen in nonpregnant patients. Amongthe 9 pregnancies, intrauterine fetaldistress was noted in 6, 7 were cesareandeliveries, and 6 infants were born pre-term. Based on these limited reports andthe available data from other respiratorypathogens such as SARS and influenza, itis unknown whether pregnant womenwith COVID-19 will experience moresevere disease.

Travel guidance for pregnantwomen. Travel recommendations havebeen instituted to limit exposure topersons in the United States. All persons,including pregnant women, should nottravel to China. On Feb. 2, 2020, the USState Department upgraded their traveladvisory to level 4, the highest level oftravel advisory. Obstetric providers

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should obtain a detailed travel history forall patients and should specifically askabout travel in the past 14 days to areasexperiencing widespread transmission ofSARS-CoV-2. Currently this is limited toChina, but this situation is rapidlyevolving and obstetricians should stayalert to the global situation byconsulting the Centers for DiseaseControl and Prevention website andfollowing media coverage.

Vaccination in pregnancy. There iscurrently no vaccine to prevent COVID-19. Since posting of a SARS-CoV-2 virusgenetic sequence online on Jan. 10, 2020,multiple organizations, including theNational Institutes of Health, have beenworking to rapidly develop a COVID-19 vaccine. Development of thisvaccine builds on and benefits fromwork on SARS and MERS vaccines.46

However, it is not known how quickly asafe and effective vaccine may bereadily available.

Infection control measures anddiagnostic testing. All patients,including pregnant women, should beevaluated for fever and signs and symp-toms of a respiratory infection. Ideally,screening procedures begin beforearrival on a labor and delivery unit orprenatal care clinic. For example, when

BOX 2Principles for management of pregnant women with confirmed or suspected COVID-1948,53,54,a

� Patients with respiratory symptoms should adhere to respiratory hygiene, cough etiquette, and hand hygiene. Ensure rapid triage ofpregnant patients with respiratory symptoms. Patients with respiratory symptoms should wear a facemask and wait in a separate, well-ventilated waiting area at least 6 feet from other people.

� Confirmed and suspected cases of COVID-19 should be isolated as soon as possible in an AIIR. If an AIIR is not available, considertransfer to a hospital with an AIIR.

� Implement CDC infection prevention and control procedures for health care providers including standard, contact, and airborneprecautions. Eye protection and properly fitted N95 respirators should be used. Provide additional staff training in correct use ofpersonal protective equipment including correct donning, doffing, and disposal of personal protective equipment.

� Contact hospital infection personnel.� In coordination with local/state health department, collect and send relevant specimens for diagnostic SARS-CoV-2 testing.� Limit visitor and health care personnel access to patient rooms with a confirmed or suspected case.� Pregnancy should be considered a potentially increased risk condition and monitored closely including fetal heart rate and contraction

monitoring.

� Consider early oxygen therapy (target O2 saturations �95% and/or pO2 �70 mm Hg). Consider early mechanical ventilation withevidence of advancing respiratory failure. Noninvasive ventilation techniques may have a small increased risk of aspiration inpregnancy.

� Use intravenous fluids conservatively unless cardiovascular instability is present.� Screen for other viral respiratory infections and bacterial infections (because of risk of coinfections).� Consider empiric antimicrobial therapy (because of risk for superimposed bacterial infections).� Consider empiric treatment for influenza, pending diagnostic testing.� Do not routinely use corticosteroids. Use of steroids to promote fetal maturity with anticipated preterm delivery can be considered on

individual basis.

� If septic shock is suspected, institute prompt, targeted management.� Delivery and pregnancy termination decisions should be based on gestational age, maternal condition, and fetal stability, and maternal

wishes.

� Consult with specialists in obstetrics, maternal-fetal medicine, neonatology, intensive care, anesthesia, and nursing.� Communicate with patients and families regarding diagnosis, clinical status, and management wishes.

AIIR, airborne infection isolation room; CDC, Centers for Disease Control and Prevention; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

a All guidance should be considered subject to revision as additional data on pregnant women with COVID-19 become available.

Rasmussen. 2019 novel coronavirus and pregnancy. Am J Obstet Gynecol 2020.

ajog.org Expert Review

scheduling appointments, patientsshould be instructed what to do if theyhave respiratory symptoms on the day oftheir appointment, or if a patient callstriage prior to presentation, respiratorysigns and symptoms should be assessedover the telephone.

Those patients with respiratorysymptoms should be separated fromother waiting patients and a facemaskshould be placed on them. Patients whomeet criteria for a person under inves-tigation (Box 1) should be immediatelyplaced in an airborne infection isolationroom (single-patient rooms at negativepressure). Once in isolation, the patient’sfacemask may be removed. Health carepersonnel should adhere to standard,contact, and airborne precautions.Infection control personnel and local/

state health departments should benotified immediately; local/state healthdepartments can help to arrange testingof relevant specimens (upper and lowerrespiratory specimens and serum arecurrently recommended; other speci-mens [stool and urine]may also be sent).

Management of COVID-19 inpregnancy.General principlesregarding management of COVID-10during pregnancy include earlyisolation, aggressive infection controlprocedures, testing for SARS-CoV-2and coinfection, oxygen therapy asneeded, avoidance of fluid overload,empiric antibiotics (because ofsecondary bacterial infection risk), fetaland uterine contraction monitoring,early mechanical ventilation for

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progressive respiratory failure,individualized delivery planning, and ateam-based approach withmultispecialty consultations (Box 2).

Team-based management is recom-mended for pregnancies managed in ahealth care facility and should include adetermination of the optimal clinicalunit on which to provide care. Ability toprovide surveillance for early detectionof aworseningmaternal course of illness,as well as an ability to monitor for evi-dence of obstetric complications (eg,preterm labor or fetal compromise), areneeded.

Changes in fetal heart rate patternmay be an early indicator of maternalrespiratory deterioration. Based onexperience with SARS and MERS, se-vere respiratory failure might occur in

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pregnant women, and in the most se-vere cases, mechanical ventilationmight not be sufficient to supportadequate oxygenation. If that occurs,limited literature suggests a potentialrole of extracorporeal membraneoxygenation in pregnancy; use shouldbe considered only in centers that haveexperience with this technique.47

Whether delivery provides benefit to acritically ill mother is unknown; de-cisions regarding delivery shouldconsider the gestational age of the fetusand should be made in conjunctionwith the neonatologist.48

There are currently no antiviral med-ications approved by the US Food andDrug Administration for treatment ofCOVID-19, although broad-spectrumantivirals used in animal models ofMERS are being evaluated for activityagainst SARS-CoV-2.46 Corticosteroidsfor the treatment of coronavirus-associated pneumonia should be avoi-ded unless other indications are presentbecause they were not shown to bebeneficial in MERS and could lead todelayed MERS-CoV clearance.49 There-fore, decisions about the use of cortico-steroids for fetal lung maturity should bemade in consultation with infectiousdisease specialists and maternal-fetalmedicine consultants. All guidanceshould be considered subject to revisionas additional data on pregnant womenwith COVID-19 become available.

Care of infants born to mothers withCOVID-19. Although the limitedexperience with newborn evaluationsafter delivery with SARS and MERShas not identified cases of maternal-to-fetal transmission, reports haveappeared in the media of a 30 hourinfant who was diagnosed withCOVID-19, suggesting the possibilityof in utero transmission.50 However,insufficient information is includedin media reports to rule out perinatalor postnatal modes of transmission.

Data from the recent case series pub-lished by Chen et al44 and Zhu et al45 of18 women (19 infants) infected in thethird trimester of pregnancy with SARS-CoV-2 identified no laboratory evidenceof vertical transmission. Testing of

10 American Journal of Obstetrics & Gynecology

amniotic fluid, cord blood, and neonatalthroat swab samples was negative forSARS-CoV-2 in the 6 patients reportedby Chen et al.44

In the report by Zhu et al.,45 someinfants were symptomatic (shortness ofbreath in 6, cyanosis in 3, gastricbleeding in 2, and 1 baby died ofmultipleorgan failure and DIC); however, throatswab testing of all infants was negativefor SARS-CoV-2 , suggesting that theseneonatal complications might not berelated intrauterine transmission. Thus,at this time, it is unknown whetherSARS-CoV-2 can be transmitted frommother-to-fetus.Given the current lack of informa-

tion, it seems reasonable to assume thata newborn born to a mother withCOVID-19 at delivery could possibly beinfected, either in utero or perinatally,and thus should be placed in isolation toavoid exposure to other newborns.Although the ideal setting for a healthyinfant is within a healthy mother’sroom, temporary separation of an illmother and her infant, as was recom-mended during pandemic H1N1,51

seems prudent.Whether COVID-19 can be trans-

mitted through breastmilk is unknown.We are aware of a single report of SARS-CoV testing of breastmilk in a motherwho had recovered from SARS and noviral RNA was detected; however, thespecimen was collected w130 days afterillness onset.15 SARS-CoV antibodieswere seen in breastmilk of that patient15

but not in another patient who wasinfected at 7 weeks’ gestation withbreastmilk tested at postpartum days 12and 30.16 Breastmilk was tested forSARS-CoV-2 in 6 of the mothers re-ported by Chen et al44; all specimenswere negative.Until additional data are available,

mothers who intend to breastfeed andare well enough to express breastmilkshould be encouraged to do so; breast-feeding can be instituted after she is nolonger considered infectious. No dataare available to guide length of separa-tion and will need to be decided on acase-by-case basis after discussion be-tween infection control experts andneonatologists.

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ConclusionsThe COVID-19 outbreak is rapidlyincreasing in the number of cases,deaths, and countries affected. Much isunknown about the virus and its effects,including its modes of transmission, thebasic reproduction number, risk factorsfor illness, and case fatality rate.Although cases are primarily in China, itis highly likely that there will be addi-tional global spread of the virus.

At the present time, limited data areavailable on pregnant women withCOVID-19 on which to base recom-mendations for pregnancy-specific care;however, early reports and lessons fromSARS, MERS, and other respiratory in-fections suggest that pregnant womencould have a severe clinical course. Sur-veillance systems for cases of COVID-19need to include information on preg-nancy status as well as maternal and fetaloutcomes.

It is important to be vigilant about thespread of the disease and be able toprovide rapid implementation ofoutbreak control and managementmeasures once the virus reaches a com-munity. Standard interventions tomanage any severe respiratory infectionis the foundation of care for any preg-nant woman with COVID-19 andshould be implemented aggressively in ateam-based care model. -

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